| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,, andDivision of Cardiovascular Diseases, Department of Medicine and Pharmacology, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Discovered in
the cardiac sarcolemma, ATP-sensitive
K+
(KATP) channels have more
recently also been identified within the inner mitochondrial membrane.
Yet the consequences of mitochondrial KATP channel activation on
mitochondrial function remain partially documented. Therefore, we
isolated mitochondria from rat hearts and used
K+ channel openers to examine the
effect of mitochondrial KATP
channel opening on mitochondrial membrane potential, respiration, ATP generation, Ca2+ transport, and
matrix volume. From a mitochondrial membrane potential of 
180 ± 15 mV, K+ channel openers,
pinacidil (100 µM), cromakalim (25 µM), and levcromakalim (20 µM), induced membrane depolarization by 10 ± 7, 25 ± 9, and
24 ± 10 mV, respectively. This effect was abolished by removal of
extramitochondrial K+ or
application of a KATP channel
blocker. K+ channel opener-induced
membrane depolarization was associated with an increase in the rate of
mitochondrial respiration and a decrease in the rate of mitochondrial
ATP synthesis. Furthermore, treatment with a
K+ channel opener released
Ca2+ from mitochondria preloaded
with Ca2+, an effect also
dependent on extramitochondrial K+
concentration and sensitive to
KATP channel blockade. In
addition, K+ channel openers,
cromakalim and pinacidil, increased matrix volume and released
mitochondrial proteins, cytochrome c
and adenylate kinase. Thus, in isolated cardiac mitochondria,
KATP channel openers depolarized
the membrane, accelerated respiration, slowed ATP production, released
accumulated Ca2+, produced
swelling, and stimulated efflux of intermembrane proteins. These
observations provide direct evidence for a role of mitochondrial KATP channels in regulating
functions vital for the cardiac mitochondria.
heart; mitochondria; potassium channel openers; calcium
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
THE POTASSIUM ION is the major cytoplasmic and mitochondrial cation, and net flux of K+ across the inner mitochondrial membrane critically regulates mitochondrial activity (16). This includes regulation of energy production and maintenance of cellular Ca2+ homeostasis, two mitochondrial functions essential for cellular survival (12, 15, 23, 24). To allow for bidirectional K+ cycling across an otherwise K+-impermeable inner membrane, mitochondria express specialized K+ conduits (16). These include the well-characterized electroneutral K+/H+ antiporter responsible for K+ efflux, along with less known pathways for K+ influx (8, 15).
A candidate mechanism for K+ entry is an ATP-sensitive K+ (KATP) channel (15, 16). This channel, known as the mitochondrial KATP channel, has been recently identified within the inner mitochondrial membrane (29), and the molecular identity of channel subunits has been partially characterized (16, 59, 60). Purified channel proteins, when incorporated into artificial bilayers or liposomes, reconstitute an ATP-sensitive K+ conductance with properties similar to those previously described for other members of the KATP channel family (52). This channel family regroups nucleotide-gated inwardly rectifying K+ channels, which sense the metabolic state of a cell and regulate K+ flux and membrane excitability (1, 2, 31, 42, 46, 59, 67).
KATP channels have been originally described in the cardiac sarcolemma (50), and opening of sarcolemmal KATP channels has been associated with shortening of cardiac action potential, decrease in intracellular Ca2+ loading, and cardioprotection during ischemia (5, 14, 20, 21, 32, 33, 44). However, the consequences of activation of mitochondrial KATP channels on mitochondrial functions, including oxidative phosphorylation and Ca2+ transport, have not been determined.
K+ channel-opening drugs are the established tool used to activate KATP channels (21, 54, 66) and also target the mitochondrial KATP channels (17, 18, 61, 62). Therefore, in this study we used K+ channel openers to examine the effect of mitochondrial KATP channel opening on mitochondrial functions, including membrane potential, respiration, ATP generation, Ca2+ transport, and membrane integrity. We present evidence that activation of mitochondrial KATP channels modulates the function of isolated cardiac mitochondria.
| |
MATERIALS AND METHODS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Isolated cardiac mitochondria. Cardiac mitochondria were isolated from ether- or pentobarbital-anesthetized rats by differential centrifugation (25, 43). After thoracotomy, hearts were rapidly excised into an ice-cold isolation buffer (50 mM sucrose, 200 mM mannitol, 5 mM KH2PO4, 1 mM EGTA, 5 mM MOPS, and 0.1% BSA, pH 7.15 adjusted with KOH), atria were removed, and 1-mm3 pieces of ventricular myocardium were homogenized (30 ml of isolation buffer per heart) using a PT10/35 Polytron (Brinkman). Three 20-s homogenization cycles were performed on ice, and then the samples were centrifuged for 10 min (at 750 g) using a Sorvall II centrifuge equipped with a GSA rotor. The supernatant, containing the mitochondrial fraction, was further centrifuged at 7,000 g for 20 min, and the pellet was resuspended in 30 ml of isolation buffer (with no EGTA) and spun at 7,000 g for 20 min. Finally, mitochondria were resuspended in the isolation buffer (with no EGTA), and protein concentration was determined using a protein kit (Bio-Rad). Mitochondrial suspension (~30-40 mg protein/ml) was kept on ice before experiments.
Mitochondrial membrane potential.
Measurements were made at 30°C under continuous stirring of the
mitochondrial suspension (1 mg protein/ml incubation medium) placed
into a multichannel chamber of an ESON-6ch computerized analyzer
(25-28). The standard incubation medium contained (in mM) 110 KCl,
5 K2HPO4,
5 succinate, 5 pyruvate, and 10 MOPS (pH 7.15). Mitochondrial membrane
potential was measured with tetraphenylphosphonium (TPP+)-sensitive minielectrodes
manufactured and calibrated as described elsewhere (38).
TPP+ (200 nM) was added to the
incubation medium in the chamber before addition of mitochondria, and
mitochondrial membrane potential was calculated according to the
following equation: 
= 59 × log (v/V) 59 × log
[10(E 
E0)/59 1], where is mitochondrial membrane potential
(mV), v is mitochondrial matrix volume (1.6 µl/mg mitochondrial
protein) (53), V is volume of incubation medium (1 ml), and
E0 and
E are electrode potentials before and
after addition of mitochondria, respectively (49). Membrane potential
was measured in the presence of K+
channel openers [pinacidil (RBI), cromakalim (Sigma Chemical), and levcromakalim (a gift from SmithKline Beecham)],
K+ ionophore (valinomycin),
and/or K+ channel blockers
[glyburide and 5-hydroxydecanoic acid (5-HD), both from
RBI]. In addition, mitochondrial membrane potential was also
measured after addition of ADP, in the absence and presence of a
K+ channel opener.
Mitochondrial respiration. O2 consumption of mitochondria was measured in the multichannel chamber using a calibrated Clark-type O2 minielectrode (11, 25). For calibration purposes, depletion of O2 content within the mitochondrial suspension was achieved by sodium hydrosulfite. Data acquisition and processing were the same as with the TPP+ electrode. The effects of drugs were assessed on "state 2" mitochondrial respiration (7). In addition, in certain experiments, ADP-stimulated mitochondrial respiration ("state 3") was measured in the absence and presence of a K+ channel opener.
Mitochondrial Ca2+ uptake. Mitochondrial Ca2+ uptake was measured as a change in the free Ca2+ concentration within the suspension using calibrated Ca2+-selective minielectrodes (Microelectrodes) (11, 26, 28). Data acquisition and processing were the same as with the TPP+ electrode. The effect of K+ channel openers on mitochondrial Ca2+ retention and release was studied in mitochondria preloaded with Ca2+ (3 consecutive 40-nmol Ca2+ pulses/mg mitochondrial protein).
Mitochondrial ATP synthesis. Mitochondrial ATP content was determined in mitochondrial extracts (9). Briefly, 200 µl of mitochondrial suspension were treated with 20 µl of 3.3 M HClO4, and precipitated proteins were removed by centrifugation (60 s, 14,000 rpm, 4°C). After neutralization of the supernatant with 80 µl of a mixture containing 2.5 M K2CO3 in 1 M HEPES, the precipitate was separated by centrifugation (60 s, 14,000 rpm, 4°C), and the concentration of ATP within the extract was determined by coupled enzymatic analysis based on spectrophotometric detection of NADH (40) in the absence and presence of a K+ channel opener.
Mitochondrial volume and integrity. Light scattering of mitochondrial suspensions, a measure of matrix volume (18, 24, 25), was determined within a 10-mm cuvette (maintained at 22°C) in the presence of K+ channel openers or a K+ ionophore. The absorbance of the mitochondrial suspension was measured at 540 nm using a spectrophotometer (model DU-7400, Beckman).
The integrity of the mitochondrial membrane, in the absence and presence of K+ channel openers, was assessed by measuring release of cytochrome c and adenylate kinase, two intermembrane proteins (47, 56). Supernatants, obtained after sedimentation (at 14,000 g, 15 min, 4°C) of the mitochondrial suspension, were concentrated by ultrafiltration (Centricon 3, Amicon), and an aliquot (30 µl) was immobilized on nitrocellulose membranes (Optitran BA-NC) using a Minifold I dot-blot system. Membrane dot blots were probed with a mouse anti-cytochrome c monoclonal antibody (clone 6H2.B4, Pharmingen) and detected with a rabbit anti-mouse IgG conjugated with horseradish peroxidase (Amersham), which served as a secondary antibody. The blot was placed on the SuperSignal CL-HRP substrate (Pierce) and exposed to an X-Omat film (Eastman Kodak) for 60 s. Adenylate kinase activity was determined within the supernatant spectrophotometrically (9, 10, 40).| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Effect on mitochondrial membrane potential.
Isolated cardiac mitochondria had a membrane potential of 180 ± 15 mV (n = 12), as demonstrated
using a potential-sensitive probe,
TPP+ (Fig.
1A).
Mitochondria maintained a steady membrane potential throughout the
duration of recordings (up to 40 min). Addition of the
K+ channel opener pinacidil (100 µM) induced rapid depolarization (Fig.
1A). On average, mitochondrial
membrane potential decreased by 10 ± 7 mV
(n = 5) in the presence of
100 µM pinacidil. The effect of pinacidil was concentration dependent
(Fig. 1B). The K+ ionophore valinomycin (12.5 ng/mg mitochondrial protein) also reduced mitochondrial membrane
potential, indicating that depolarization can be triggered by promoting
K+ flux across the mitochondrial
membrane (Fig. 1A).
|
|
|
|
Effect on mitochondrial respiration.
The rate of state 2 respiration of isolated cardiac
mitochondria was 14.0 ± 1.3 nmol
O2 · min1 · mg
protein1
(n = 20). Pinacidil (100 µM-1
mM), in a concentration-dependent manner, induced an increase in the
rate of mitochondrial respiration (Fig.
5A).
Pretreatment (3-5 min) of mitochondria with the
KATP channel blocker glyburide (1 µM) inhibited the effect of pinacidil on mitochondrial respiration
(Fig. 5B;
n = 3).
|
1 · mg
protein1 in the absence and
presence of pinacidil, respectively) without changing the total amount
of the ADP-stimulated O2
consumption, which was 340 ± 10 and 353 ± 8 natoms in the
absence and presence of the K+
channel opener (n = 3; Fig. 6).
|
Effect on mitochondrial ATP synthesis.
Isolated cardiac mitochondria efficiently phosphorylated ADP (500 µM)
so that ~90% of added ADP was converted to ATP within 100 ± 15 s
(n = 3; Fig.
7). The initial rate of ATP synthesis was
401 ± 35 nmol
ATP · min1 · mg
protein1, and the half-time
required for complete conversion of added ADP to ATP was 27 ± 5 s
(n = 3; Fig. 7). Pinacidil (100 µM)
decreased the rate of initial ATP synthesis to 187 ± 23 nmol
ATP · min1 · mg
protein1 and increased the
half-time required for conversion of ADP to ATP to 87 ± 7 s
(n = 3; Fig. 7). Although the rate of
mitochondrial synthesis was slowed, pinacidil (100 µM) did not
prevent conversion of ADP to ATP (Fig. 7).
|
Effect on mitochondrial Ca2+ loading. Mitochondria are known to accumulate and to retain Ca2+ within the matrix (22). Isolated cardiac mitochondria efficiently took up and retained added Ca2+ when repeatedly challenged with extramitochondrial Ca2+ pulses (in total 120 nmol Ca2+/mg mitochondrial protein; Fig. 8). Addition of pinacidil (250 µM) induced rapid release of Ca2+ from preloaded mitochondria (Fig. 8, A-C). The efficacy of pinacidil to induce release of mitochondrial Ca2+ was dependent on the extramitochondrial concentration of K+ (Fig. 8, A-C). At 1, 10, and 110 mM extramitochondrial KCl, the magnitude of pinacidil-induced Ca2+ release was 1, 3, and 5 nmol Ca2+/mg mitochondrial protein, respectively (Fig. 8, A-C). The Ca2+-releasing effect of pinacidil (250 µM) was suppressed by pretreatment of mitochondria with the KATP channel blocker glyburide (1 µM; Fig. 8D).
|
Effect on mitochondrial matrix volume and integrity. The volume of mitochondria depends on the permeability of the inner membrane to osmotically active particles, such as K+ (6). The K+ channel opener cromakalim (100 µM) induced swelling of mitochondria, as revealed by a decrease in the absorbance of the mitochondrial suspension in K+-containing media by 0.1 ± 0.02 optical density unit (n = 3; Fig. 9A). Under this condition, the K+ ionophore valinomycin also induced significant mitochondrial swelling (not shown). In contrast, in K+-free medium, cromakalim had no significant effect on mitochondrial swelling (Fig. 9; n = 3). K+-dependent changes in mitochondrial volume were also observed with pinacidil (250 µM; Fig. 9B).
|
|
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
In the present study we report that, in mitochondria isolated from cardiac muscle, K+ channel openers induced membrane depolarization, accelerated respiration, slowed ATP production, triggered release of Ca2+, and produced swelling associated with efflux of intermembrane proteins. In accord with an activation of mitochondrial KATP channels, these effects were dependent on the extramitochondrial concentration of K+, were inhibited by blockers of KATP channels, and could be induced by structurally distinct K+ channel openers. These observations provide direct evidence for a role of mitochondrial KATP channels in the regulation of mitochondrial functions.
That KATP channels are present
within the inner membrane of mitochondria was initially demonstrated on
the basis of electrophysiological measurements of a
K+-selective, ATP-gated ion
conductance in fused giant mitoplasts (29). The presence of functional
KATP channels in mitochondria was
confirmed after isolation of an inner membrane protein fraction from
rat liver and beef heart mitochondria, which, when reconstituted in
liposomes or planar lipid bilayers, catalyzed electrophoretic ATP-sensitive K+ flux (52). This
ATP-inhibited K+ flux was
activated by K+ channel openers
such as cromakalim (18) and suppressed by
K+ channel blockers such as
glyburide and 5-HD (3, 17, 51, 63).
K+ influx through this channel was
hypothesized to serve as a mechanism for osmotic regulation of
mitochondrial volume (15, 23, 29, 62). In mitochondria from noncardiac
tissue, such as liver and pancreatic 
-cells, openers of
KATP channels were found to affect mitochondrial energy metabolism (16, 19, 63). Thus the present findings
that opening of mitochondrial KATP
channels can modulate multiple functions in isolated cardiac
mitochondria provide direct evidence for a
KATP channel-mediated regulation
of cardiac mitochondrial behavior.
Pinacidil, cromakalim, and levcromakalim share the property to activate
KATP channels (21, 54, 66) and
were found here to depolarize the membrane potential of cardiac
mitochondria. However, it has remained controversial whether opening of
mitochondrial KATP channels can be
associated with changes in mitochondrial membrane potential (19, 61).
In pancreatic -cells, glyburide, a
KATP channel blocker, failed to
antagonize the depolarizing effect of diazoxide, a drug with multiple
sites of action, including K+
channel activation, suggesting that diazoxide-induced membrane depolarization is not associated with activation of
KATP channels, at least in this
cell type (19). Moreover, in isolated liver mitochondria, other
K+ channel openers, including
aprikalim and nicorandil, were without effect on membrane potential,
although in the same preparation, RP-66471, a more recently developed
KATP channel opener, induced mitochondrial depolarization (61).
Here, in cardiac mitochondria, a
KATP channel-mediated regulation
of mitochondrial membrane potential is supported by three lines of
evidence. First, structurally distinct
K+ channel openers were effective
in depolarizing mitochondria. Second, the effect of
K+ channel openers on
mitochondrial membrane potential was dependent on the electrochemical
gradient for K+. Third, 5-HD, a
selective KATP channel blocker
(51), did not affect membrane potential by itself but prevented the
depolarizing action of a K+
channel opener. Our findings are in accord with the property of
cromakalim and other K+ channel
openers to induce K+ flux through
mitochondrial KATP channels (18).
Under the present experimental condition (110 mM extramitochondrial
K+ and = 180 mV),
opening of KATP channels is
expected to lead to K+ influx and
depolarization of mitochondria. In turn, a decrease in membrane
potential would dissipate the driving force for ATP synthesis,
triggering a compensatory activation of the mitochondrial respiratory
chain. It has previously been shown that increase in the
K+ permeability by valinomycin of
the inner membrane decreases the rate of ATP synthesis and promotes
respiration (53). The present study extends this concept and shows that
activation of KATP channels not
only induces membrane depolarization but can also reduce the rate of
ATP synthesis and increase O2
consumption in cardiac mitochondria.
In addition to energy production, mitochondria have the capacity to store Ca2+, a function critical in the maintenance of cellular Ca2+ homeostasis (13). In the present study, isolated cardiac mitochondria, when challenged with repeated Ca2+ pulses, displayed the property to accumulate and store Ca2+. Opening of mitochondrial KATP channels rapidly released Ca2+ from preloaded mitochondria, an effect also seen with K+ ionophores. Although the precise mechanism for such an effect on Ca2+ release is unknown, the sensitivity toward KATP channel blockade and the dependence on extramitochondrial K+ concentration are in line with a KATP channel-mediated membrane depolarization and promotion of Ca2+ release. Such interpretation also concurs with the notion that setting the mitochondrial membrane potential is critical for cyclic accumulation and release of Ca2+ (30).
In the present study we further demonstrated that opening of mitochondrial KATP channels increased matrix volume, which is manifested through mitochondrial swelling. This finding supports previous reports that mitochondrial KATP channels can regulate the osmotic status of the mitochondrial matrix (15, 16). Depending on the extent of swelling, an increase in matrix volume may also lead to a change in the permeability of the outer membrane to macromolecules that are located within the intermembrane (47, 58). In this regard, the present observation, that opening of K+ channels could induce release of intermembrane proteins, is suggestive of a significant increase in matrix volume and of a possible compromise in the integrity of the mitochondrial membrane.
In summary, the present study provides direct evidence that opening of mitochondrial KATP channels modulates essential functions of isolated cardiac mitochondria. The cellular consequences of mitochondrial KATP channel opening are not known. It has been proposed that this ion conductance may participate in the protection of cardiac muscle from ischemia-reperfusion injury (17). Because mitochondrial Ca2+ overload is implicated in cellular injury (13), our findings may suggest a possible beneficial effect of mitochondrial KATP channel opening through regulation of mitochondrial Ca2+ levels. The present study also identifies a KATP channel-mediated decrease in the rate of ATP synthesis and a release of mitochondrial proteins. Because a decrease in cellular ATP content coupled with the presence of cytochrome c within the cytosol has been associated with cellular apoptosis (48, 56), this further suggests that opening of mitochondrial KATP channels may participate in the regulation of cellular viability. The net effect of opening of mitochondrial KATP channels is, however, difficult to predict in view of the diversity in cellular protective mechanisms (20, 21, 34, 35, 44, 57) and the complex nature of KATP channel gating (2, 4, 16, 36, 65). Indeed, it is still controversial whether in excitable tissues opening of K+ channels leads to programmed cell death (68) or promotes cellular survival (17, 20, 41).
| |
ACKNOWLEDGEMENTS |
|---|
This research was supported by National Heart, Lung, and Blood Institute Grant HL-0711-22, a Merck Sharp & Dohme International Award in Clinical Pharmacology, and grants from the American Heart Association, the Miami Heart Research Institute, and the Bruce and Ruth Rappaport Program in Vascular Biology and Gene Delivery.
| |
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: A. Terzic, Div. of Cardiovascular Diseases, Dept. of Medicine, Guggenheim-7F, Mayo Clinic and Foundation, Rochester, MN 55905.
Received 23 April 1998; accepted in final form 2 July 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
1.
Aguilar-Bryan, L.,
J. P. Clement,
G. Gonzales,
K. Kunjilwar,
A. Babenko,
and
J. Bryan.
Toward understanding the assembly and structure of KATP channels.
Physiol. Rev.
78:
227-245,
1998
2.
Alekseev, A. E.,
P. A. Brady,
and
A. Terzic.
Ligand-insensitive state of cardiac ATP-sensitive K+ channels. Basis for channel opening.
J. Gen. Physiol.
111:
381-394,
1998
3.
Belyaeva, E. A.,
A. Szewczyk,
B. Mikolajek,
M. J. Nalecz,
and
L. Wojtczak.
Demonstration of glibenclamide-sensitive K+ fluxes in rat liver mitochondria.
Biochem. Mol. Biol. Int.
31:
493-500,
1993[Medline].
4.
Brady, P. A.,
A. E. Alekseev,
and
A. Terzic.
Operative condition-dependent response of cardiac ATP-sensitive K+ channels toward sulfonylureas.
Circ. Res.
82:
272-278,
1998
5.
Brady, P. A.,
S. Zhang,
J. R. Lopez,
A. Jovanovic,
A. E. Aleeksev,
and
A. Terzic.
Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes.
Eur. J. Pharmacol.
308:
343-349,
1996[Medline].
6.
Brierley, G. P.
The uptake and extrusion of monovalent cations by isolated heart mitochondria.
Mol. Cell. Biochem.
10:
41-62,
1976[Medline].
7.
Chance, B.,
and
G. R. Williamson.
The respiratory chain and phosphorylation.
Adv. Enzyme Regul.
17:
65-134,
1955.
8.
Diwan, J. J.
Mitochondrial transport of K+ and Mg2+.
Biochim. Biophys. Acta
895:
155-165,
1987[Medline].
9.
Dzeja, P. P.,
R. J. Zeleznikar,
and
N. D. Goldberg.
Suppression of creatine kinase-catalyzed phosphotransfer results in increased phosphoryl transfer by adenylate kinase in intact skeletal muscle.
J. Biol. Chem.
271:
12847-12851,
1996
10.
Elvir-Mairena, J. R.,
A. Jovanovic,
L. A. Gomez,
A. E. Alekseev,
and
A. Terzic.
Reversal of the ATP-liganded state of ATP-sensitive K+ channels by adenylate kinase activity.
J. Biol. Chem.
271:
31903-31908,
1996
11.
Evtodienko, Y. V.,
V. P. Zinchenko,
E. L. Holmuhamedov,
A. V. Gylkhandanyan,
and
A. M. Zhabotinsky.
The stoichiometry of ion fluxes in oscillating mitochondria.
Biochim. Biophys. Acta
589:
157-161,
1980[Medline].
12.
Ferrari, R.
The role of mitochondria in ischemic heart disease.
J. Cardiovasc. Pharmacol.
28:
S1-S10,
1996.
13.
Ferrari, R.,
P. Pedersini,
M. Bongrazio,
G. Gaia,
P. Bernocchi,
F. Di Lisa,
and
O. Visioli.
Mitochondrial energy production and cation control in myocardial ischemia and reperfusion.
Basic Res. Cardiol.
88:
495-512,
1993[Medline].
14.
Findlay, I.
Interactive regulation of the ATP-sensitive potassium channel of cardiac muscle.
J. Cardiovasc. Pharmacol.
24:
S6-S11,
1994.
15.
Garlid, K. D.
Cation transport in mitochondria.
Biochim. Biophys. Acta
1275:
123-126,
1996[Medline].
16.
Garlid, K. D.
Physiology of mitochondria.
In: Cell Physiology. Source Book, edited by N. Sperelakis. New York: Academic, 1998, p. 111-118.
17.
Garlid, K. D.,
P. Paucek,
V. Yarov-Yarovoy,
H. N. Murray,
R. B. Darbenzio,
A. J. D'Alonzo,
N. J. Lodge,
M. A. Smith,
and
G. J. Grover.
Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels.
Circ. Res.
81:
1072-1082,
1997
18.
Garlid, K. D.,
P. Paucek,
V. Yarov-Yarovoy,
X. Sun,
and
P. Schindler.
The mitochondrial KATP channel as a receptor for potassium channel openers.
J. Biol. Chem.
271:
8796-8799,
1996
19.
Grimmsmann, T.,
and
I. Rustenbeck.
Direct effect of diazoxide on mitochondria in pancreatic B-cells and on isolated liver mitochondria.
Br. J. Pharmacol.
123:
781-788,
1998[Medline].
20.
Gross, G. J.
ATP-sensitive potassium channels and myocardial preconditioning.
Basic Res. Cardiol.
90:
85-88,
1995[Medline].
21.
Grover, G. J.
Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of myocardial ischemia and reperfusion.
Can. J. Physiol. Pharmacol.
75:
309-315,
1997[Medline].
22.
Gunter, T. E.,
K. K. Gunter,
S. Sheu,
and
C. E. Gavin.
Mitochondrial calcium transport: physiological and pathological relevance.
Am. J. Physiol.
267 (Cell Physiol. 36):
C313-C339,
1994
23.
Halestrap, A. P.
Regulation of mitochondrial metabolism through changes in matrix volume.
Biochem. Soc. Trans.
22:
522-529,
1994[Medline].
24.
Halestrap, A. P.
The regulation of the matrix volume mammalian mitochondria in vitro and its role in control of mitochondrial metabolism.
Biochim. Biophys. Acta
973:
355-382,
1979.
25.
Holmuhamedov, E. L.
Oscillating dissipative structures in mitochondrial suspension.
Eur. J. Biochem.
158:
543-546,
1986[Medline].
26.
Holmuhamedov, E. L.,
E. A. Chukhlova,
V. V. Teplova,
V. P. Zinchenko,
and
Y. V. Evtodienko.
Excitability of inner mitochondrial membrane. Irreversible increase in mitochondrial membrane K+ permeability by divalent cations.
Biol. Membr.
5:
866-872,
1988.
27.
Holmuhamedov, E. L.,
V. V. Teplova,
E. A. Chukhluva,
Y. V. Evtodienko,
and
R. G. Urlich.
Strontium excitability of the inner mitochondrial membrane: regenerative strontium-induced strontium release.
Biochem. Mol. Biol. Int.
36:
39-49,
1995[Medline].
28.
Ichas, F.,
L. S. Jouaville,
S. S. Sidash,
J. P. Mazat,
and
E. L. Holmuhamedov.
Mitochondrial calcium spiking: a transduction mechanism based on calcium-induced permeability transition involved in cell calcium signalling.
FEBS Lett.
348:
211-215,
1994[Medline].
29.
Inoue, I.,
H. Nagase,
K. Kishi,
and
T. Higuti.
ATP-sensitive K+ channel in the mitochondrial inner membrane.
Nature
352:
244-247,
1991[Medline].
30.
Jouaville, L. S.,
F. Ichas,
E. L. Holmuhamedov,
P. Camacho,
and
J. D. Lechleiter.
Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes.
Nature
377:
438-441,
1995[Medline].
31.
Jovanovic, A.,
A. E. Alekseev,
and
A. Terzic.
Intracellular diadenosine polyphosphates: a novel family of inhibitory ligands of the ATP-sensitive K+ channel.
Biochem. Pharmacol.
54:
219-225,
1997[Medline].
32.
Jovanovic, A.,
S. Jovanovic,
E. Lorenz,
and
A. Terzic.
Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance towards chemical hypoxia-reoxygenation injury.
Circulation
98:
1548-1555,
1998
33.
Jovanovic, A.,
S. Jovanovic,
D. C. Mays,
J. J. Lipsky,
and
A. Terzic.
Diadenosine 5',5
-P1,P5-pentaphosphate harbors the properties of a signaling molecule in the heart.
FEBS Lett.
423:
314-318,
1998[Medline].
34.
Jovanovic, A.,
J. R. Lopez,
A. E. Alekseev,
W. K. Shen,
and
A. Terzic.
Adenosine prevents K+-induced Ca2+ loading: insight into cardioprotection during cardioplegia.
Ann. Thorac. Surg.
65:
586-591,
1998
35.
Jovanovic, A.,
J. R. Lopez,
and
A. Terzic.
Cytosolic Ca2+ domain-dependent protective action of adenosine in cardiomyocytes.
Eur. J. Pharmacol.
298:
63-69,
1996[Medline].
36.
Jovanovic, A.,
S. Zhang,
A. E. Alekseev,
and
A. Terzic.
Diadenosine polyphosphate-induced inhibition of cardiac KATP channels: operative state-dependent regulation by a nucleoside diphosphate.
Pflügers Arch.
431:
800-802,
1996[Medline].
37.
Jung, D. W.,
E. Chavez,
and
G. P. Brierley.
Energy-dependent exchange of K+ in heart mitochondria.
Arch. Biochem. Biophys.
183:
452-459,
1977[Medline].
38.
Kamo, N.,
M. Muratsugu,
R. Hongoh,
and
Y. Kobatake.
Membrane potential measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state.
J. Membr. Biol.
49:
105-121,
1979[Medline].
39.
Kluck, R. M.,
E. Bossy-Wetzel,
D. R. Green,
and
D. D. Newmayer.
The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis.
Science
275:
1132-1136,
1997
40.
Krause, S. M.,
and
W. E. Jacobus.
Specific enhancement of the cardiac myofibrillar ATPase by bound creatine kinase.
J. Biol. Chem.
267:
2480-2486,
1992
41.
Lauritzen, I.,
J. R. De Weille,
and
M. Lazdunski.
The potassium channel opener ()-cromakalim prevents glutamate-induced cell death in hippocampal neurons.
J. Neurochem.
69:
1570-1579,
1997[Medline].
42.
Lazdunski, M.
ATP-sensitive potassium channels: an overview.
J. Cardiovasc. Pharmacol.
24:
S1-S5,
1994.
43.
Lesnefsky, E. J.,
B. Tandler,
J. Ye,
T. J. Slabe,
J. Turkaly,
and
C. L. Hoppel.
Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria.
Am. J. Physiol.
273 (Heart Circ. Physiol. 42):
H1544-H1554,
1997
44.
Lopez, J. R.,
R. A. Ghanbari,
and
A. Terzic.
A KATP channel opener protects cardiomyocytes from Ca2+ waves: a laser confocal microscopy study.
Am. J. Physiol.
270 (Heart Circ. Physiol. 39):
H1384-H1389,
1996
45.
Lopez, J. R.,
A. Jovanovic,
and
A. Terzic.
Spontaneous calcium waves without contraction in cardiac myocytes.
Biochem. Biophys. Res. Commun.
214:
781-787,
1995[Medline].
46.
Lorenz, E.,
A. E. Alekseev,
G. B. Krapivinsky,
A. J. Carrasco,
D. E. Clapham,
and
A. Terzic.
Evidence for direct physical association between a K+ channel (Kir6.2) and an ABC protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K+ channel.
Mol. Cell. Biol.
18:
1652-1659,
1998
47.
MacLennan, D. H.,
G. Lenaz,
and
L. Szarkovska.
Studies on the mechanism of oxidative phosphorylation. IX. Effect of cytochrome c on energy-linked processes.
J. Biol. Chem.
241:
5251-5259,
1996
48.
Marton, A.,
R. Mihalik,
A. Bratincsak,
V. Adleff,
I. Petak,
M. Vegh,
P. I. Bauer,
and
P. Krajcsi.
Apoptotic cell death induced by inhibitors of energy conservation.
Eur. J. Biochem.
250:
467-475,
1997[Medline].
49.
Murutsagu, M.,
N. Kamo,
K. Kurihaara,
and
Y. Kobatake.
Selective electrode for dibenzyl dimethyl ammonium cation as indicator of the membrane potential in biological systems.
Biochim. Biophys. Acta
464:
613-619,
1977[Medline].
50.
Noma, A.
ATP-regulated K+ channels in cardiac muscle.
Nature
305:
147-148,
1983[Medline].
51.
Notsu, T.,
I. Tanaka,
M. Takano,
and
A. Noma.
Blockade of the ATP-sensitive K+ channel by 5-hydroxydecanoate in guinea pig ventricular myocytes.
J. Pharmacol. Exp. Ther.
260:
702-708,
1992
52.
Paucek, P.,
G. D. Mironova,
F. Mahdi,
A. D. Beavis,
G. Woldergiorgis,
and
K. D. Garlid.
Reconstitution and partial purification of the glybenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria.
J. Biol. Chem.
267:
26062-26069,
1992
53.
Petronili, V.,
D. Pietrobon,
M. Zoratti,
and
G. F. Azzone.
Free energy coupling between H+-generating and H+-consuming pumps.
Eur. J. Biochem.
155:
423-431,
1986[Medline].
54.
Quast, U.,
and
N. S. Cook.
Moving together: K+ channel openers and ATP-sensitive K+ channels.
Trends Pharmacol. Sci.
10:
431-434,
1989[Medline].
55.
Rauch, U.,
K. Schulze,
B. Witzenbichler,
and
H. P. Schulthesiss.
Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia contributes to early contractile failure.
Circ. Res.
75:
760-769,
1994
56.
Reed, J. C.
Cytochrome c: can't live with it
can't live without it.
Cell
91:
559-562,
1997[Medline].
57.
Romashko, D. N.,
E. Marban,
and
B. O'Rourke.
Subcellular metabolic transients and mitochondrial redox waves in heart cells.
Proc. Natl. Acad. Sci. USA
95:
1618-1623,
1998
58.
Schnaitman, C.,
and
J. W. Greenawalt.
Enzymatic properties of the inner and outer membranes of rat liver mitochondria.
J. Cell Biol.
38:
158-175,
1968
59.
Seino, S.,
N. Inagaki,
N. Namba,
and
T. Gonoi.
Molecular biology of the -cell ATP-sensitive K+ channel.
Diabetes Rev.
4:
177-190,
1996.
60.
Suzuki, M.,
K. Kotake,
K. Fujikura,
N. Inagaki,
T. Suzuki,
T. Gonoi,
S. Seino,
and
K. Takata.
Kir6.1. A possible subunit of ATP-sensitive K+ channels in mitochondria.
Biochem. Biophys. Res. Commun.
241:
693-697,
1997[Medline].
61.
Szewczyk, A.
Intracellular targets for antidiabetic sulfonylureas and potassium channel openers.
Biochem. Pharmacol.
54:
961-965,
1997[Medline].
62.
Szewczyk, A.,
A. Czyz,
G. Wojcik,
L. Wojczak,
and
M. Nalecz.
ATP-regulated K+ channel in mitochondria: pharmacology and function.
J. Bioenerg. Biomembr.
28:
147-152,
1996[Medline].
63.
Szewczyk, A.,
G. Wojcik,
N. A. Lobanov,
and
M. J. Nalecz.
The mitochondrial sulfonylurea receptor: identification and characterization.
Biochem. Biophys. Res. Commun.
230:
611-615,
1997[Medline].
64.
Szewczyk, A.,
G. Wojcik,
and
M. Nalecz.
Potassium channel opener, RP 66471, induces membrane depolarization of rat liver mitochondria.
Biochem. Biophys. Res. Commun.
207:
126-132,
1995[Medline].
65.
Terzic, A.,
I. Findlay,
Y. Hosoya,
and
Y. Kurachi.
Dualistic behavior of ATP-dependent K+ channel towards intracellular nucleoside diphosphates.
Neuron
12:
1049-1058,
1994[Medline].
66.
Terzic, A.,
A. Jahangir,
and
Y. Kurachi.
Cardiac ATP-sensitive K+ channel regulation by intracellular nucleotides and K+channel opening drugs.
Am. J. Physiol.
269 (Cell Physiol. 38):
C525-C545,
1995
67.
Terzic, A.,
R. T. Tung,
and
Y. Kurachi.
Nucleotide regulation of ATP sensitive potassium channels.
Cardiovasc. Res.
28:
746-753,
1996.
68.
Yu, S. P.,
C. H. Yeh,
S. L. Sensi,
B. J. Gwag,
L. M. T. Canzoniero,
Z. S. Fahrangrazi,
H. S. Ying,
M. Tian,
L. l. Dugan,
and
D. W. Choi.
Mediation of neuronal apoptosis by enhancement of outward potassium current.
Science
278:
114-117,
1997
This article has been cited by other articles:
|
|
 |
|
  L. Argaud, O. Gateau-Roesch, L. Augeul, E. Couture-Lepetit, J. Loufouat, L. Gomez, D. Robert, and M. Ovize Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H386 - H391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jahangir, S. Sagar, and A. Terzic Aging and cardioprotection J Appl Physiol, December 1, 2007; 103(6): 2120 - 2128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shinohara, N. Takahashi, H. Kohno, K. Yamanaka, T. Ooie, O. Wakisaka, Y. Murozono, Y. Taniguchi, Y. Torigoe, M. Hara, et al. Mitochondria are targets for geranylgeranylacetone-induced cardioprotection against ischemia-reperfusion in the rat heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1892 - H1899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. T. Nguyen, S. J. Dudycha, and M. S. Jafri Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2004 - C2020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Heinen, A. K. S. Camara, M. Aldakkak, S. S. Rhodes, M. L. Riess, and D. F. Stowe Mitochondrial Ca2+-induced K+ influx increases respiration and enhances ROS production while maintaining membrane potential Am J Physiol Cell Physiol, January 1, 2007; 292(1): C148 - C156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kaasik, D. Safiulina, A. Zharkovsky, and V. Veksler Regulation of mitochondrial matrix volume Am J Physiol Cell Physiol, January 1, 2007; 292(1): C157 - C163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Stowe, M. Aldakkak, A. K. S. Camara, M. L. Riess, A. Heinen, S. G. Varadarajan, and M.-T. Jiang Cardiac mitochondrial preconditioning by Big Ca2+-sensitive K+ channel opening requires superoxide radical generation Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H434 - H440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Krolikowski, M. Bienengraeber, D. Weihrauch, D. C. Warltier, J. R. Kersten, and P. S. Pagel Inhibition of Mitochondrial Permeability Transition Enhances Isoflurane-Induced Cardioprotection During Early Reperfusion: The Role of Mitochondrial KATP Channels Anesth. Analg., December 1, 2005; 101(6): 1590 - 1596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Chapman, S. E. Sinclair, D. Zhuang, A. Hassid, L. P. Desai, and C. M. Waters Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L834 - L841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gomez, N. Chavanis, L. Argaud, L. Chalabreysse, O. Gateau-Roesch, J. Ninet, and M. Ovize Fas-independent mitochondrial damage triggers cardiomyocyte death after ischemia-reperfusion Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2153 - H2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kimura, G.-X. Zhang, A. Nishiyama, T. Shokoji, L. Yao, Y.-Y. Fan, M. Rahman, and Y. Abe Mitochondria-Derived Reactive Oxygen Species and Vascular MAP Kinases: Comparison of Angiotensin II and Diazoxide Hypertension, March 1, 2005; 45(3): 438 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. I. Gursahani and S. Schaefer Acidification reduces mitochondrial calcium uptake in rat cardiac mitochondria Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2659 - H2665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Ludwig, K. Tanaka, J. T. Eells, D. Weihrauch, P. S. Pagel, J. R. Kersten, and D. C. Warltier Preconditioning by Isoflurane Is Mediated by Reactive Oxygen Species Generated from Mitochondrial Electron Transport Chain Complex III Anesth. Analg., November 1, 2004; 99(5): 1308 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rousou, M. Ericsson, M. Federman, S. Levitsky, and J. D. McCully Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1967 - H1976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Han, H. Long, H. Wang, J. Wang, Y. Zhang, and Z. Wang Progressive apoptotic cell death triggered by transient oxidative insult in H9c2 rat ventricular cells: a novel pattern of apoptosis and the mechanisms Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2169 - H2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Remillard and J. X.-J. Yuan Activation of K+ channels: an essential pathway in programmed cell death Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L49 - L67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Meana, D. Garcia-Dorado, P. Pina, J. Inserte, L. Agullo, and J. Soler-Soler Cariporide preserves mitochondrial proton gradient and delays ATP depletion in cardiomyocytes during ischemic conditions Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H999 - H1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Jain, R. B. Schuessler, and J. E. Saffitz Mechanisms of Delayed Electrical Uncoupling Induced by Ischemic Preconditioning Circ. Res., May 30, 2003; 92(10): 1138 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Baumann, S. Poitry, A. Roatti, and A. J. Baertschi Plasmalemmal KATP channels shape triggered calcium transients in metabolically impaired rat atrial myocytes Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2296 - H2305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Loubani and M. Galinanes Long-term administration of nicorandil abolishes ischemic and pharmacologic preconditioning of the human myocardium: Role of mitochondrial adenosine triphosphate-dependent potassium channels J. Thorac. Cardiovasc. Surg., October 1, 2002; 124(4): 750 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wakiyama, D. B. Cowan, Y. Toyoda, M. Federman, S. Levitsky, and J. D. McCully Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis Eur. J. Cardiothorac. Surg., March 1, 2002; 21(3): 424 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Szewczyk and L. Wojtczak Mitochondria as a Pharmacological Target Pharmacol. Rev., March 1, 2002; 54(1): 101 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xu, Y. Wang, A. Ayub, and M. Ashraf Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1295 - H1303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, J. H. Traverse, J. Zhang, and R. J. Bache Selective blockade of mitochondrial KATP channels does not impair myocardial oxygen consumption Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H738 - H744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Haller, S. L. Mironov, and D. W. Richter Intrinsic Optical Signals in Respiratory Brain Stem Regions of Mice: Neurotransmitters, Neuromodulators, and Metabolic Stress J Neurophysiol, July 1, 2001; 86(1): 412 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, G. Cherednichenko, L. Hernandez, J. Halow, S. A. Camacho, V. Figueredo, and S. Schaefer Preconditioning limits mitochondrial Ca2+ during ischemia in rat hearts: role of KATP channels Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2321 - H2328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Korge, H. M. Honda, and J. N. Weiss Regulation of the mitochondrial permeability transition by matrix Ca2+ and voltage during anoxia/reoxygenation Am J Physiol Cell Physiol, March 1, 2001; 280(3): C517 - C526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Kowaltowski, S. Seetharaman, P. Paucek, and K. D. Garlid Bioenergetic consequences of opening the ATP-sensitive K+ channel of heart mitochondria Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H649 - H657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xu, Y. Wang, K. Hirai, A. Ayub, and M. Ashraf Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H899 - H908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, J. Cone, and Y. Liu Dual roles of mitochondrial KATP channels in diazoxide-mediated protection in isolated rabbit hearts Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H246 - H255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O'Rourke Myocardial KATP Channels in Preconditioning Circ. Res., November 10, 2000; 87(10): 845 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Eells, M. M. Henry, G. J. Gross, and J. E. Baker Increased Mitochondrial KATP Channel Activity During Chronic Myocardial Hypoxia : Is Cardioprotection Mediated by Improved Bioenergetics? Circ. Res., November 10, 2000; 87(10): 915 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Headrick, N. S. Gauthier, R. Morrison, and G. P. Matherne Cardioprotection by KATP channels in wild-type hearts and hearts overexpressing A1-adenosine receptors Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1690 - H1697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Matar, T. M. Nosek, D. Wong, and J.-M. Renaud Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue Am J Physiol Cell Physiol, February 1, 2000; 278(2): C404 - C416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Fryer, J. T. Eells, A. K. Hsu, M. M. Henry, and G. J. Gross Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H305 - H312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sato Signaling in Late Preconditioning : Involvement of Mitochondrial KATP Channels Circ. Res., December 3, 1999; 85(12): 1113 - 1114. [Full Text] [PDF]
|
|
|
|
|
|
E. Takashi, Y. Wang, and M. Ashraf Activation of Mitochondrial KATP Channel Elicits Late Preconditioning Against Myocardial Infarction via Protein Kinase C Signaling Pathway Circ. Res., December 3, 1999; 85(12): 1146 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Domoki, J. V. Perciaccante, R. Veltkamp, F. Bari, D. W. Busija, and R. M. Bryan Jr Mitochondrial Potassium Channel Opener Diazoxide Preserves Neuronal-Vascular Function After Cerebral Ischemia in Newborn Pigs • Editorial Comment Stroke, December 1, 1999; 30(12): 2713 - 2719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O’Rourke Apoptosis : Rekindling the Mitochondrial Fire Circ. Res., November 12, 1999; 85(10): 880 - 883. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tanonaka, T. Taguchi, M. Koshimizu, T. Ando, T. Morinaka, T. Yogo, F. Konishi, and S. Takeo Role of an ATP-Sensitive Potassium Channel Opener, YM934, in Mitochondrial Energy Production in Ischemic/Reperfused Heart J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 710 - 716. [Abstract] [Full Text]
|
|
|
|
|
|
G. J. Gross and R. M. Fryer Sarcolemmal Versus Mitochondrial ATP-Sensitive K+ Channels and Myocardial Preconditioning Circ. Res., May 14, 1999; 84(9): 973 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Jovanovic and A. TERZIC Gene delivery of Kir6.2/SUR2A in conjunction with pinacidil handles intracellular Ca2+ homeostasis under metabolic stress FASEB J, May 1, 1999; 13(8): 923 - 929. [Abstract] [Full Text]
|
|
|
|
|
|
R. M. Fryer, A. K. Hsu, J. T. Eells, H. Nagase, and G. J. Gross Opioid-Induced Second Window of Cardioprotection : Potential Role of Mitochondrial KATP Channels Circ. Res., April 16, 1999; 84(7): 846 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Forbes, C. Steenbergen, and E. Murphy Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism Circ. Res., April 27, 2001; 88(8): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Imahashi, T. Nishimura, J. Yoshioka, and H. Kusuoka Role of Intracellular Na+ Kinetics in Preconditioned Rat Heart Circ. Res., June 8, 2001; 88(11): 1176 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Akao, A. Ohler, B. O'Rourke, and E. Marban Mitochondrial ATP-Sensitive Potassium Channels Inhibit Apoptosis Induced by Oxidative Stress in Cardiac Cells Circ. Res., June 22, 2001; 88(12): 1267 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Minners, L. Lacerda, J. McCarthy, J. J. Meiring, D. M. Yellon, and M. N. Sack Ischemic and Pharmacological Preconditioning in Girardi Cells and C2C12 Myotubes Induce Mitochondrial Uncoupling Circ. Res., October 26, 2001; 89(9): 787 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. X. Zhang, Y.-F. Chen, W. B. Campbell, A.-P. Zou, G. J. Gross, and P.-L. Li Characteristics and Superoxide-Induced Activation of Reconstituted Myocardial Mitochondrial ATP-Sensitive Potassium Channels Circ. Res., December 7, 2001; 89(12): 1177 - 1183. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
