A-Kinase Anchoring Protein 9 and I_Ks Channel Regulation

Abstract

A-kinase anchoring proteins (AKAPs) create compartmentalized environment inside the cell to bring various signaling molecules to their targets. In the heart, a slowly activating potassium channel (I_Ks) important for cardiac repolarization is tightly regulated by the sympathetic nervous system in an AKAP-dependent manner. I_Ks channel forms a macromolecular complex with AKAP9 and other enzymes, such as protein kinase A, phosphatase, adenylyl cyclase, and phosphodiesterase, all of which are responsible to control the phosphorylation state of the channel. Such a complex thus ensures the I_Ks channel to be regulated properly to maintain the normal cardiac rhythm. Disruptions of various elements of the complex have been found to cause severe pathological consequences, including the long QT syndrome.