Characterization of the Transmural Myocardial Electrocardiographic Response in in Vivo Canine Working Hearts under Reduced Flow and Increased Heart Rate

Cardiac K+ channels are cardiomyocyte membrane proteins that regulate K+ ion flow across the cell membrane on the electrochemical gradient and determine the resting membrane potential and the cardiac action potential morphology and duration. Several K+ channels have been well studied in the human heart. They include the transient outward K+ current Ito1, the ultra-rapidly activating delayed rectifier current IKur, the rapidly and slowly activating delayed rectifier currents IKr and IKs, the inward rectifier K+ current IK1, and ligand-gated K+ channels, including adenosine-5’-triphosphate (ATP)-sensitive K+ current (IKATP) and acetylcholine-activated current (IKACh). Regional differences of K+ channel expression contribute to the variable morphologies and durations of cardiac action potentials from sinus node and atrial to ventricular myocytes, and different ventricular layers from endocardium and midmyocardium to epicardium. They also show different responses to endogenous regulators and/or pharmacological agents. K+ channels are well-known targets for developing novel anti-arrhythmic drugs that can effectively prevent/inhibit cardiac arrhythmias. Especially, atrial-specific K+ channel currents (IKur and IKACh) are the targets for developing atrial-selective anti-atrial fibrillation drugs, which has been greatly progressed in recent years. This chapter concentrates on recent advances in intracellular signaling regulation and pharmacology of cardiac K+ channels under physiological and pathophysiological conditions.