Autonomic regulation of delayed rectifier K+ current in mammalian heart involves G proteins.

The role of adrenergic and cholinergic stimulation in regulating the delayed outward K+ current (IK) was examined by using isolated guinea pig ventricular myocytes. Isoproterenol (ISO) stimulated IK in a reversible manner. Similar effects were seen by directly stimulating adenylate cyclase with forskolin (FSK). The responses to ISO and FSK were reversed by concurrent application of acetylcholine (ACh), but ACh alone did not affect IK. When a nonhydrolyzable analogue of guanosine 5'-triphosphate was introduced intracellularly, in the presence of extracellular ISO, IK was irreversibly stimulated. In cells pretreated with pertussis toxin the ACh response was blocked. These results suggest that autonomic regulation of IK is similar to that of the Ca2+ current and involves guanine nucleotide-binding proteins. This has important implications with respect to autonomic control of action potential duration and pacemaker activity in the heart.