G-PROTEIN REGULATION OF CARDIAC MUSCARINIC POTASSIUM CHANNEL

Several ion channels can be regulated by G proteins in a ''membrane-delimited'' manner. The cardiac muscarinic K+ (K-ACh) channel, which is responsible for the acetylcholine (ACh) or adenosine-induced deceleration of heart beat and atrioventricular conduction, is the prototype of this type of receptor-dependent regulation of ion channels. Because similar transduction mechanisms are utilized by various membrane receptors, such as somatostatin, 5-hydroxytryptamine-1, alpha(2)-adrenergic, mu- and delta-opioid, D-2-dopamine, and gamma-aminobutyric acid B receptors, in neuronal, hormone-secreting, renal, or smooth muscle cells, the G protein (G(K))-K-ACh channel system illustrates the principles underlying one of the most important cell signaling mechanisms (B. Hille. Neuron 9: 187-195, 1992). It seems that both alpha- and beta gamma-subunits of G(K) may be involved in the regulation of the K-ACh channel of mammalian atrial muscle. A general consensus of opinion has emerged, after some years of controversy, to support the notion that physiological activation of the channel by G(K) is the responsibility of the beta gamma-subunits. Recent evidence suggests that the K-ACh channel interacts with the alpha-subunit in the terminating process of activation.