EFFECTS OF NITRIC-OXIDE ON FORCE-GENERATING PROTEINS OF SKELETAL-MUSCLE

Nitric oxide (NO) has recently been identified as a physiologically im portant intracellular messenger modulating the contractile activity of skeletal muscle [Kobzik L, Reid MB, Bredt DS, Stamler JS (1994) Natur e 372: 546-548]. However, the mechanism of action of NO is not yet kno wn, We used skinned (demembranated) muscle fibres to investigate the m echanism of NO function in muscle contraction. Maximally Ca2+-activate d 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) a ctivity. These results reveal a novel molecular mechanism of NO action : a direct inhibition of the force-generating proteins in skeletal mus cle.