Interaction between sympathetic activation and the calcium channel

Acceleration of sinus node automaticity by sympathetic stimulation results from an increase in the influx of sodium (If) during diastolic depolarization and an increase in calcium (Ca++) influx during phase 0; both are due to a direct stimulatory effect of the alpha subunit of the guanosine nucleotide binding protein (G protein) on the respective channels. In the resting nonstimulated state (panel A) guanosine diphosphate is bound to the alpha subunit of the G protein. With beta receptor activation (panel B), guanosine triphosphate (GTP) displaces GDP, stimulating adenyl cyclase; this generates cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) (panel C). Generation of cAMP activates protein kinase A and phosphorylation of the regulatory component of the CA++ channel; the opening of the Ca++ channel in response to membrane depolarization is increased. Activation of the alpha subunit of the G protein may also activate the Ca++ channel. With deactivation of the beta receptor, an intrinsinc GTPase hydrolyzes GTP to GDP (panel D).