Regulation of the slow inward current appears to be an important mechanism by which the autonomic nervous system modifies cardiac function. Beta-adrenergic stimulation augments the slow inward current by increasing the number of functional slow inward current channels. This effect is mediated by cyclic adenosine monophosphate (cyclic AMP) and presumably involves phosphorylation of membrane proteins associated with the slow channels. Beta antagonists (propranolol) act by inhibiting beta-adrenergic activation of adenylate cyclase and thereby prevent increases in cyclic AMP. The calcium channel antagonists (verapamil) act directly at the level of the slow channels to inhibit the slow inward current independent of changes in cyclic AMP. Cholinergic stimulation attenuates beta-adrenergic stimulation of the slow inward current by one or both of two potential mechanisms: reduction in cyclic AMP formation and antagonism of the distal effects of cyclic AMP.