Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function

Ekshon L. Holmuhamedov, Sofija Jovanović, Petras P Dzeja, Aleksandar Jovanović, Andre Terzic

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume44
Issue number5
StatePublished - Nov 1998

Fingerprint

KATP Channels
Cromakalim
Adenosine Triphosphate
Pinacidil
Mitochondria
Mitochondrial Membrane Potential
Membranes
Respiration
Adenylate Kinase
Heart Mitochondria
Sarcolemma
Mitochondrial Proteins
Mitochondrial Membranes
Respiratory Rate
Cytochromes c
mitochondrial K(ATP) channel
Proteins

Keywords

  • Calcium
  • Heart
  • Mitochondria
  • Potassium channel openers

ASJC Scopus subject areas

  • Physiology

Cite this

Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function. / Holmuhamedov, Ekshon L.; Jovanović, Sofija; Dzeja, Petras P; Jovanović, Aleksandar; Terzic, Andre.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 44, No. 5, 11.1998.

Research output: Contribution to journalArticle

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