Caffeine increases resting calcium influx approximately threefold in normally polarized and in potassium-depolarized fibers of frog sartorius muscles. It does not affect the transient rapid increase in calcium influx that occurs at the beginning of a potassium depolarization. Calcium outflux in Ringer's solution, in zero calcium Ringer's solution, and in zero calcium Ringer's solution plus 0.004 M EDTA is also markedly increased by caffeine. The increased outflux reaches a rate which is approximately the same as the increased calcium influx. One interpretation of the findings is that caffeine reduces the binding of calcium both in the membrane and in the myoplasm; this increases the "permeability" to calcium and the ionic activity of calcium in muscle. This interpretation is consistent with the view that the contractile state of muscle is dependent at least in part on the thermodynamic activity of calcium in the muscle fibers.

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