HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/H1820    most recent 00589.2004v2 00589.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Saotome, M. Articles by Hayashi, H. Search for Related Content PubMed PubMed Citation Articles by Saotome, M. Articles by Hayashi, H.

Mitochondrial membrane potential modulates regulation of mitochondrial Ca²⁺ in rat ventricular myocytes

Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Submitted 15 June 2004 ; accepted in final form 18 November 2004

Although recent studies focused on the contribution of mitochondrial Ca²⁺ to the mechanisms of ischemia-reperfusion injury, the regulation of mitochondrial Ca²⁺ under pathophysiological conditions remains largely unclear. By using saponin-permeabilized rat myocytes, we measured mitochondrial membrane potential (_m) and mitochondrial Ca²⁺ concentration ([Ca²⁺]_m) at the physiological range of cytosolic Ca²⁺ concentration ([Ca²⁺]_c; 300 nM) and investigated the regulation of [Ca²⁺]_m during both normal and dissipated _m. When _m was partially depolarized by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP, 0.01–0.1 µM), there were dose-dependent decreases in [Ca²⁺]_m. When complete _m dissipation was achieved by FCCP (0.3–1 µM), [Ca²⁺]_m remained at one-half of the control level despite no Ca²⁺ influx via the Ca²⁺ uniporter. The _m dissipation by FCCP accelerated calcein leakage from mitochondria in a cyclosporin A (CsA)-sensitive manner, which indicates that _m dissipation opened the mitochondrial permeability transition pore (mPTP). After FCCP addition, inhibition of the mPTP by CsA caused further [Ca²⁺]_m reduction; however, inhibition of mitochondrial Na⁺/Ca²⁺ exchange (mitoNCX) by a Na⁺-free solution abolished this [Ca²⁺]_m reduction. Cytosolic Na⁺ concentrations that yielded one-half maximal activity levels for mitoNCX were 3.6 mM at normal _m and 7.6 mM at _m dissipation. We conclude that 1) the mitochondrial Ca²⁺ uniporter accumulates Ca²⁺ in a manner that is dependent on _m at the physiological range of [Ca²⁺]_c; 2) _m dissipation opens the mPTP and results in Ca²⁺ influx to mitochondria; and 3) although mitoNCX activity is impaired, mitoNCX extrudes Ca²⁺ from the matrix even after _m dissipation.

permeability transition pore; Na⁺/Ca²⁺ exchange; depolarization; ischemia-reperfusion injury

This article has been cited by other articles:

				M. Saotome, H. Katoh, Y. Yaguchi, T. Tanaka, T. Urushida, H. Satoh, and H. Hayashi Transient opening of mitochondrial permeability transition pore by reactive oxygen species protects myocardium from ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1125 - H1132. [Abstract] [Full Text] [PDF]

				H. Tominaga, H. Katoh, K. Odagiri, Y. Takeuchi, H. Kawashima, M. Saotome, T. Urushida, H. Satoh, and H. Hayashi Different effects of palmitoyl-L-carnitine and palmitoyl-CoA on mitochondrial function in rat ventricular myocytes Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H105 - H112. [Abstract] [Full Text] [PDF]

				E. Takahashi Anoxic cell core can promote necrotic cell death in cardiomyocytes at physiological extracellular PO2 Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2507 - H2515. [Abstract] [Full Text] [PDF]

				B. Kim and S. Matsuoka Cytoplasmic Na+-dependent modulation of mitochondrial Ca2+ via electrogenic mitochondrial Na+-Ca2+ exchange J. Physiol., March 15, 2008; 586(6): 1683 - 1697. [Abstract] [Full Text] [PDF]

				S. Belmonte and M. Morad 'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria J. Physiol., March 1, 2008; 586(5): 1379 - 1397. [Abstract] [Full Text] [PDF]

				M. E. Pamenter, D. S.-H. Shin, M. Cooray, and L. T. Buck Mitochondrial ATP-sensitive K+ channels regulate NMDAR activity in the cortex of the anoxic western painted turtle J. Physiol., February 15, 2008; 586(4): 1043 - 1058. [Abstract] [Full Text] [PDF]

				M. Ljubkovic, Y. Mio, J. Marinovic, A. Stadnicka, D. C. Warltier, Z. J. Bosnjak, and M. Bienengraeber Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1583 - C1590. [Abstract] [Full Text] [PDF]

				M. Sedova, E. N. Dedkova, and L. A. Blatter Integration of rapid cytosolic Ca2+ signals by mitochondria in cat ventricular myocytes Am J Physiol Cell Physiol, November 1, 2006; 291(5): C840 - C850. [Abstract] [Full Text] [PDF]

				M. Ruiz-Meana, D. Garcia-Dorado, E. Miro-Casas, A. Abellan, and J. Soler-Soler Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion Cardiovasc Res, September 1, 2006; 71(4): 715 - 724. [Abstract] [Full Text] [PDF]