Calcineurin-dependent ion channel regulation in heart

Calcineurin, a serine-threonine-specific, Ca²⁺-calmodulin-activated protein phosphatase, conserved from yeast to humans, plays a key role in regulating cardiac development, hypertrophy, and pathological remodeling. Recent studies demonstrate that calcineurin regulates cardiomyocyte ion channels and receptors in a manner which often entails direct interaction with these target proteins. Here, we review the current state of knowledge of calcineurin-mediated regulation of ion channels in the myocardium with emphasis on the transient outward potassium current (I_to) and L-type calcium current (I_Ca,L). We go on to discuss unanswered questions that surround these observations and provide perspective on future directions in this exciting field.