Time- and use-dependent inhibition by ryanodine of caffeine-induced contraction of guinea-pig aortic smooth muscle.

We examined how ryanodine interfered with Ca2+-releasing action of caffeine in guinea-pig aorta. Ryanodine (10 microM) decreased the caffeine-induced contraction depending on the time of pretreatment with the agent. The development of ryanodine-effect with time was neither due to a slow access to its binding site nor due to the depletion of stored Ca2+. Ryanodine more potently inhibited the second or the subsequent contraction due to caffeine than the first one even after the agent was removed from the bath after first caffeine. The enhancement of ryanodine-effect depended on the history of Ca2+ release but not on an increase in cytoplasmic Ca2+. The data suggest that an opening of Ca2+ release channel enhances the interaction of ryanodine with the channel.