Stimulation of the slow calcium current in bullfrog skeletal muscle fibers by cAMP and cGMP.

The effects of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) on slow calcium currents (ICa) were investigated using the Vaseline-gap voltage-clamp technique in bullfrog skeletal muscle cut fibers. Both cAMP and cGMP induced a pronounced increase in the amplitude of ICa when applied to the cut ends of fibers. Both cyclic nucleotides also decreased time to peak current at all membrane potentials. The current-voltage relationship was shifted toward more negative potentials by cAMP as well as cGMP. The potentiating effects of cAMP and cGMP on ICa were additive. 8-Bromo analogues of both nucleotides had similar effects on ICa. The beta-adrenergic agonist isoproterenol, applied extracellularly, also produced an increase in the amplitude of ICa and produced a leftward shift in the current-voltage relationship. These results suggest that both cAMP and cGMP modulate calcium slow channels in bullfrog skeletal muscle fibers, causing stimulation of the ICa. The effect of cyclic nucleotides on ICa in bullfrog skeletal muscle contrasts with that in mammalian cardiac muscle, in which the same nucleotides produce opposite effects on the slow ICa, i.e., in cardiac muscle cAMP stimulates, and cGMP inhibits, the slow ICa.