Voltage-gated potassium (Kv) channels play an important role in regulating cardiac muscle excitability by controlling action potential duration and frequency. Essential for this activity is proper localization and organization of the cardiac Kv channels in specific microdomains of the plasma membrane. The underlying processes involve tight control of anterograde and retrograde Kv channel trafficking into and out of the plasma membrane. Thus, cardiac Kv channel density at the cell surface is regulated by a dynamic interplay of endocytotic and recycling pathways, the mechanisms of which are mostly unknown. Recent studies have indicated that the lipid composition in the Kv channel surround profoundly influences these processes. Local differences in lipid composition altering the mechanic state of the lipid bilayer or a specific interaction with an important domain of the Kv channel markedly affect voltage-sensitive gating, clustering, and mobility of cardiac Kv channels and, thereby, the excitability in the healthy and diseased heart muscles.
