Effects of nitric oxide on force-generating proteins of skeletal muscle.
Nitric oxide (NO) has recently been identified as a physiologically important intracellular messenger modulating the contractile activity of skeletal muscle [Kobzik L, Reid MB, Bredt DS, Stamler JS (1994) Nature 372: 546-548]. However, the mechanism of action of NO is not yet known. We used skinned (demembranated) muscle fibres to investigate the mechanism of NO function in muscle contraction. Maximally Ca2+-activated single fibres of rat skeletal muscle were exposed to physiologically relevant NO concentrations by adding NO donor molecules into the bath solution. Donor application caused a decline both in the contractile properties and in the myofibrillar adenosine triphosphatase (ATPase) activity. These results reveal a novel molecular mechanism of NO action: a direct inhibition of the force-generating proteins in skeletal muscle.
Galler
S
S
Department of Animal Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria.
Hilber
K
K
Göbesberger
A
A
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine
D004791:Enzyme Inhibitors; D009124:Muscle Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000251:Adenosine Triphosphatases; D010396:Penicillamine; D002118:Calcium