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 guanosi ne 3',5'-cyclic monophosphate (cGMP) on slow calcium currents (I(Ca)) were investigated using the Vaseline-gap voltage-clamp technique in bu llfrog skeletal muscle cut fibers. Both cAMP and cGMP induced a pronou nced increase in the amplitude of I(Ca) when applied to the cut ends o f fibers. Both cyclic nucleotides also decreased time to peak current at all membrane potentials. The current-voltage relationship was shift ed toward more negative potentials by cAMP as well as cGMP. The potent iating effects of cAMP and cGMP on I(Ca) were additive. 8-Bromo analog ues of both nucleotides had similar effects on I(Ca). The beta-adrener gic agonist isoproterenol, applied extracellularly, also produced an i ncrease in the amplitude of I(Ca) and produced a leftward shift in the current-voltage relationship. These results suggest that both cAMP an d cGMP modulate calcium slow channels in bullfrog skeletal muscle fibe rs, causing stimulation of the I(Ca). The effect of cyclic nucleotides on I(Ca) in bullfrog skeletal muscle contrasts with that in mammalian cardiac muscle, in which the same nucleotides produce opposite effect s on the slow I(Ca), i.e., in cardiac muscle cAMP stimulates, and cGMP inhibits, the slow I(Ca).