Arrhythmia Protection in Hypokalemia: A Novel Role of Ca2+-Activated K+ Currents in the Ventricle
Whereas myocardial depolarization is a fast event mediated almost exclusively by rapid Na currents, myocardial repolarization is a much slower and more complex affair for the heart. It is regulated by a carefully orchestrated interplay of many different inward and outward currents that allows for a precise regulation of action potential (AP) shape and duration (Figure 1). Intact repolarization is essential for excitation-contraction coupling and helps protect the myocardium against spontaneous ectopic activity and reentrant arrhythmias. During hypokalemia, the fine balance of ion currents across the cell membrane is disrupted, resulting in action potential prolongation (Figure 2). This phenomenon, known as loss of repolarization reserve, has been also implicated in the cell pathophysiology of heart failure even during normokalemia.1 Recent reports indicate that a small-conductance Ca- activated outward K (SK) current is upregulated in failing ventricular myocytes, which partially restores repolarization reserve and AP duration.2 Since the Ca-activated K+ current is blocked by neurotoxin apamin, it is also known as apamin sensitive K current (IKAS). The molecular correlate is likely the type 2 SK channel. However, previous studies had indicated that in healthy hearts, IKAS plays a role only in atrial, but not ventricular electrophysiology.2
- Received September 4, 2015.
- Accepted September 8, 2015.