Mechanism of action of sodium cyanide on rat diaphragm muscle

The effects of sodium cyanide (NaCN) were investigated on the contractile a nd electrophysiological properties of rat diaphragm muscles in vitro, Sodiu m cyanide (0.1-1.0 mM) produced an initial potentiation of directly elicite d twitch tensions, followed by a slow progressive depression. The potentiat ion and depression were both dependent on the NaCN concentration and stimul ation frequency. Muscles exposed to NaCN exhibited marked reductions of cre atine phosphate concentration, but ATP levels were not significantly lowere d. Sodium cyanide had no effect on the resting potential, input resistance or action potential, indicating that the toxicity of the metabolic inhibito r is not mediated by alterations of membrane excitability or passive electr ical properties. Sodium cyanide reduced the amplitude of contractures elici ted by 70 mM K2SO4, suggesting that the actions of NaCN cannot be explained by a failure of action potentials to propagate across the muscle surface o r within t-tubular membranes. Sodium cyanide suppressed the first phase of the caffeine contracture, an observation consistent with an impaired releas e of, or reduced sensitivity to, sarcoplasmic reticular Ca2+, but did not a lter the amplitude of the second phase, which represents rigor following AT P depletion, These results, in conjunction with those of previous studies, suggest that the depression in muscle tension following exposure to NaCN ma y result from alterations in Ca2+ homeostasis, intracellular acidosis or fr om accumulation of one or more products of phosphocreatine breakdown. Copyr ight (C) 1999 John Whey & Sons, Ltd.