| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Pediatrics and Physiology, Biophysics Research Institute, and the Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
Peroxynitrite (ONOO
)
is a contractile agonist of rat middle cerebral arteries. To determine
the mechanism responsible for this component of ONOO
bioactivity, the present study examined the effect of
ONOO on ionic current and channel activity in rat
cerebral arteries. Whole cell recordings of voltage-clamped cells were
made under conditions designed to optimize K+ current. The
effects of iberiotoxin, a selective inhibitor of large-conductance
Ca2+-activated K+ (BK) channels, and
ONOO (10-100 µM) were determined. At a
pipette potential of +50 mV, ONOO inhibited 39% of
iberiotoxin-sensitive current. ONOO was selective
for iberiotoxin-sensitive current, whereas decomposed ONOO had no effect. In excised, inside-out membrane
patches, channel activity was recorded using symmetrical K+
solutions. Unitary currents were sensitive to increases in internal Ca2+ concentration, consistent with activity due to BK
channels. Internal ONOO dose dependently inhibited
channel activity by decreasing open probability and mean open times.
The inhibitory effect of ONOO could be overcome by
reduced glutathione. Glutathione, added after ONOO,
restored whole cell current amplitude to control levels and reverted
single-channel gating to control behavior. The inhibitory effect of
ONOO on membrane K+ current is
consistent with its contractile effects in isolated cerebral arteries
and single myocytes. Taken together, our data suggest that
ONOO has the potential to alter cerebral vascular
tone by inhibiting BK channel activity.
free radical; glutathione
This article has been cited by other articles:
|
|
 |
|
  H. Maarsingh, B. E. Bossenga, I. S. T. Bos, H. H. Volders, J. Zaagsma, and H. Meurs L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Eur. Respir. J., July 1, 2009; 34(1): 191 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takeuchi and K. Yoshii Effect of Superoxide Derived from Lucifer Yellow CH on Voltage-Gated Currents of Mouse Taste Bud Cells Chem Senses, June 1, 2008; 33(5): 425 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Bubolz, Q. Wu, B. T. Larsen, D. D. Gutterman, and Y. Liu Ebselen reduces nitration and restores voltage-gated potassium channel function in small coronary arteries of diabetic rats Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2231 - H2237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Rainbow, M. E. L. Hardy, N. B. Standen, and N. W. Davies Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells J. Physiol., September 15, 2006; 575(3): 833 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Faraci Reactive oxygen species: influence on cerebral vascular tone J Appl Physiol, February 1, 2006; 100(2): 739 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Gutterman, H. Miura, and Y. Liu Redox Modulation of Vascular Tone: Focus of Potassium Channel Mechanisms of Dilation Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 671 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, D. D. Gutterman, N. J. Rusch, A. Bubolz, and Y. Liu Nitration and Functional Loss of Voltage-Gated K+ Channels in Rat Coronary Microvessels Exposed to High Glucose Diabetes, September 1, 2004; 53(9): 2436 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Veerareddy, C.-L. M. Cooke, P. N. Baker, and S. T. Davidge Gender differences in myogenic tone in superoxide dismutase knockout mouse: animal model of oxidative stress Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H40 - H45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Grover, C.-Y. Kwan, and S. E. Samson Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCA2b and SERCA3a Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1537 - C1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, Q. Chai, D. D. Gutterman, and Y. Liu Elevated glucose impairs cAMP-mediated dilation by reducing Kv channel activity in rat small coronary smooth muscle cells Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1213 - H1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Walia, S. E. Samson, T. Schmidt, K. Best, M. Whittington, C. Y. Kwan, and A. K. Grover Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle Am J Physiol Cell Physiol, March 1, 2003; 284(3): C649 - C657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Grover, S. E. Samson, S. Robinson, and C. Y. Kwan Effects of peroxynitrite on sarcoplasmic reticulum Ca2+ pump in pig coronary artery smooth muscle Am J Physiol Cell Physiol, February 1, 2003; 284(2): C294 - C301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Frisbee, K. G. Maier, and D. W. Stepp Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2160 - H2168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, K. Terata, Q. Chai, H. Li, L. H. Kleinman, and D. D. Gutterman Peroxynitrite Inhibits Ca2+-Activated K+ Channel Activity in Smooth Muscle of Human Coronary Arterioles Circ. Res., November 29, 2002; 91(11): 1070 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, K. Terata, N. J. Rusch, and D. D. Gutterman High Glucose Impairs Voltage-Gated K+ Channel Current in Rat Small Coronary Arteries Circ. Res., July 20, 2001; 89(2): 146 - 152. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
