Opening of potassium channels modulates mitochondrial function in rat skeletal muscle.
We have investigated the presence of diazoxide- and nicorandil-activated K+ channels in rat skeletal muscle. Activation of potassium transport in the rat skeletal muscle myoblast cell line L6 caused a stimulation of cellular oxygen consumption, implying a mitochondrial effect. Working with isolated rat skeletal muscle mitochondria, both potassium channel openers (KCOs) stimulate respiration, depolarize the mitochondrial inner membrane and lead to oxidation of the mitochondrial NAD-system in a strict potassium-dependent manner. This is a strong indication for KCO-mediated stimulation of potassium transport at the mitochondrial inner membrane. Moreover, the potassium-specific effects of both diazoxide and nicorandil on oxidative phosphorylation in skeletal muscle mitochondria were completely abolished by the antidiabetic sulfonylurea derivative glibenclamide, a well-known inhibitor of ATP-regulated potassium channels (K(ATP) channels). Since both diazoxide and nicorandil facilitated swelling of de-energised mitochondria in KSCN buffer at the same concentrations, our results implicate the presence of a mitochondrial ATP-regulated potassium channel (mitoK(ATP) channel) in rat skeletal muscle which can modulate mitochondrial oxidative phosphorylation.
Debska
Grazyna
G
Laboratory of the Intracellular Ion Channels, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
Kicinska
Anna
A
Skalska
Jolanta
J
Szewczyk
Adam
A
May
Rebecca
R
Elger
Christian E
CE
Kunz
Wolfram S
WS
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002460:Cell Line; D019069:Cell Respiration / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D008293:Malates / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats
D000889:Anti-Arrhythmia Agents; D008293:Malates; D015221:Potassium Channels; D020108:Nicorandil; D018698:Glutamic Acid; C030298:malic acid; D003981:Diazoxide; D010100:Oxygen; D005905:Glyburide