A novel signalling pathway originating in mitochondria modulates rat skeletal muscle membrane excitability.
Single skeletal muscle fibres from rat and cane toad were mechanically skinned and stimulated either electrically by initiating action potentials in the sealed transverse (t-) tubular system or by ion substitution causing depolarisation of the t-system to pre-determined levels. Depression of mitochondrial ATP-producing function with three diverse mitochondrial function antagonists (azide: 1-10 mM; oligomycin 1 microg ml-1 and carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP) 1 microM), under conditions in which the cytosolic ATP was maintained high and constant, invariably reduced the excitability of rat fibres but had no obvious effect on the excitability of toad fibres, where mitochondria are less abundant and differently located. The reduction in excitability linked to mitochondria in rat fibres appears to be caused by depolarisation of the sealed t-system membrane. These observations suggest that mitochondria can regulate the functional state of mammalian muscle cells and have important implications for understanding how the balance between ATP utilisation and ATP production is regulated at the cellular level in general and in mammalian skeletal muscle fibres in particular.
Ørtenblad
Niels
N
Department of Zoology, La Trobe University, Bundoora, Melbourne, Victoria, 3086, Australia.
Stephenson
D George
DG
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002024:Bufo marinus; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D008931:Mitochondria, Muscle / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D009840:Oligomycins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012996:Solutions; D014475:Uncoupling Agents / Q000494:pharmacology
D001386:Azides; D007476:Ionophores; D009840:Oligomycins; D012996:Solutions; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase