Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function
Discovered in the cardiac sarcolemma, ATP-sensitive K+(KATP) channels have more recently also been identified withinthe inner mitochondrial membrane. Yet the consequences of mitochondrial KATP channel activation on mitochondrial function remain partially documented. Therefore, we isolated mitochondria from rathearts and used K+ channel openers to examine the effect of mitochondrial KATPchannel opening on mitochondrial membrane potential, respiration, ATP generation, Ca2+ transport, and matrix volume. From amitochondrial 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 ± 10mV, 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 anincrease 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 withCa2+, 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 andreleased mitochondrial proteins, cytochrome cand 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 functionsvital for the cardiac mitochondria.
Ekshon L. Hlmuhamedov,, Sofija Jovanovic, Preas P. Dzeja, Aleksandar Jovanovic, Andre Terzic (1998) Mitochondrial ATP-sensitive K+ channels...
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