Potential biochemical mechanisms for regulation of the slow inward current: theoretical basis for drug action.
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.
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011953:Receptors, Cyclic AMP / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D011953:Receptors, Cyclic AMP; D011433:Propranolol; D014700:Verapamil; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium