Contractures in partially depolarized muscle treated with caffeine or nitrate

Frog toe muscles partially depolarized with a subcontracture concentration (15 or 20mM) of K+ rapidly developed tension when exposed to 1 mM caffeine, which alone did not cause contracture. This action resulted from a lowering of the mechanical threshold by the caffeine and thus was similar to that caused by replacement of Cl- with NO3-. Maximal tension was the same in the caffeine and NO3- media but took much longer to develop in the former. Equilibrating the muscles with caffeine for 60 s (the time calculated for complete diffusion) did not reduce contraction time significantly. However, prolonging the exposure of muscles to caffeine beyond this time enhanced the drug's capacity to potentiate both the twitch and 30 mM K+ contractures and shortened the contraction time of the contractures. Toe muscles that had undergone a contracture in 100 mM K+ and were recovering in 15 mM K+-Ringer generated tension in the presence of 1 mM caffeine or NO3- but only after enough repolarization had been achieved so that a response to a second challenge with 100 mM K+ could be demonstrated. Although prolonged immersion in the K+-enriched recovery solution caused a disappearance of sensitivity to a test depolarization, addition of 1 mM caffeine or replacement of Cl- with NO3- promptly evoked a contracture. These results imply a reversible step in the recovery process that is both potential and time dependent. Since application of 5 mM caffeine to either normally polarized or depolarized muscles always immediately causes contracture, more than one site of action for caffeine is indicated. After disruption of the transverse tubules, partially depolarized muscles showed no response to NO3- or 1 mM caffeine but contracted vigorously when exposed to 5 mM caffeine.