MOLECULAR-BASIS OF CARDIAC POTASSIUM CHANNEL STIMULATION BY PROTEIN-KINASE-A

Cardiac beta-adrenergic receptors accelerate heart rate by modulating ionic currents through a pathway involving cyclic AMP-dependent protei n kinase A (PKA). Previous studies have focused on the regulation of C a2+ channels by PKA; however, due to the heterogeneity of K+ channels expressed within the heart, little is known about the mechanism by whi ch PKA modulates individual K+ channels. Here we report that PKA stron gly enhanced the activity of a cloned delayed rectifier K+ channel tha t is normally expressed in cardiac atria. This effect required a singl e PKA consensus phosphorylation site located near the amino terminus o f the channel protein. Furthermore, patch clamp analysis revealed that PKA phosphorylation increased the open time that single channels spen d in higher conductance states, These studies provide evidence that ho rmonal modulation of a cardiac K+ channel involves direct phosphorylat ion by PKA.