Caffeine- and potassium-induced contractures of mouse isolated soleus muscle: effects of verapamil, manganese, EGTA and calcium withdrawal.

1. The effects of verapamil, manganese, EGTA and Ca2+-withdrawal on caffeine and potassium-induced contractures of the mouse isolated soleus muscle have been studied. All four treatments profoundly inhibited, in concentration-dependent manner, both K+- and caffeine-induced contractures, and recovery from these treatments was slight. 2. Caffeine (5.14-51.4 mmol/l), elicited biphasic contractures, characterized by an initial phasic, and subsequent tonic contractures. K+-induced contractures were monophasic except at the higher concentrations (53.4-214 mmol/l), when biphasic responses were also recorded. The biphasic K+ contracture had a time course similar to the caffeine-induced response. 3. Both phases of the caffeine and K+ responses were abolished by the introduction of CA2+-free Krebs'-Henseleit solution (KHS). Increasing [Ca2+]0 from 1 to 5 mmol/l, markedly inhibited the amplitude of caffeine and K+ contractures. 4. In high [K+]0 KHS, peak contractures to caffeine were reduced to about 50% of those in normal KHS. In the presence of 15.4 mmol/l caffeine, the responses to lower concentrations of K+ (13.4-26.8 mmol/l) increased, while responses evoked by the higher K+ concentrations were depressed compared with controls in normal KHS. 5. Pancuronium or D-tubocurarine severely inhibited caffeine-induced contractures, but only slightly inhibited K+-induced responses. 6. It is suggested that both caffeine- and K+-induced contractures of the mouse soleus are dependent upon the presence of [Ca2+]0, and that these contractures possibly occurred as a result of extracellular Ca2+-influx.