Effects of dantrolene and D2O on K+-stimulated respiration of skeletal muscle.

We have examined the effects of dantrolene and D2O on the K+-stimulated respiration in frog skeletal muscle. The threshold for K+ stimulation was around 10 mM extracellular potassium concentration ([K+]o). A further marked increase in respiration to levels about ten times the resting level was noted when [K+]o was between 15 and 20 mM. The increase was sustained for hours when [K+]o was less than 20 mM; however, with higher concentrations the stimulation consisted of an initial burst followed by a decline. Dantrolene shifted the relationship between [K+]o and peak increase in respiration toward higher [K+]o by about 10 mM; in addition it nearly completely blocked the sustained component of the increase. D2O, nearly abolished the K+-induced respiration. Neither agent shifted the relationship between [K+]o and membrane potential nor abolished the stimulation of respiration caused by caffeine. Dantrolene did not block the stimulation of Na+ efflux caused by 15 mM K+. The results with these agents are consistent with the proposal that K+-stimulated respiration is due to Ca2+ release into the cytoplasm. In addition, they provide evidence that the stimulated rate of Ca2+ release into the cytoplasm can remain at a persistently high level for hours provided [K+]o does not exceed 20 mM. We calculated that the level of this constant Ca2+ release is about 3.4 X 10(16) ions/(s.cm3).