TY - JOUR
T1 - Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function
AU - Holmuhamedov, Ekshon L.
AU - Jovanović, Sofija
AU - Dzeja, Petras P.
AU - Jovanović, Aleksandar
AU - Terzic, Andre
PY - 1998/11
Y1 - 1998/11
N2 - Discovered in the cardiac sarcolemma, ATP-sensitive K+ (K(ATP)) channels have more recently also been identified within the inner mitochondrial membrane. Yet the consequences of mitochondrial K(ATP) 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 K(ATP) 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 K(ATP) 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 KATe 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, K(ATP) 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 K(ATP) channels in regulating functions vital for the cardiac mitochondria.
AB - Discovered in the cardiac sarcolemma, ATP-sensitive K+ (K(ATP)) channels have more recently also been identified within the inner mitochondrial membrane. Yet the consequences of mitochondrial K(ATP) 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 K(ATP) 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 K(ATP) 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 KATe 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, K(ATP) 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 K(ATP) channels in regulating functions vital for the cardiac mitochondria.
KW - Calcium
KW - Heart
KW - Mitochondria
KW - Potassium channel openers
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U2 - 10.1152/ajpheart.1998.275.5.h1567
DO - 10.1152/ajpheart.1998.275.5.h1567
M3 - Article
C2 - 9815062
AN - SCOPUS:33750712460
SN - 0363-6135
VL - 275
SP - H1567-H1576
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5 44-5
ER -