Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?

Abstract

The shape of the cardiac action potential (AP) is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP) and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention. In this review we present the current evidence for the mechanisms which underlie precise control of cardiac ion channel trafficking and targeting.

Keywords: accessory proteins; arrhythmias; cardiac; potassium channels; sodium channel; trafficking.

Figure 1

General scheme of the various steps and regulators involved in the trafficking of ion channels. Ion channels are targeted to the plasma membrane via the anterograde and recycling pathways (red arrows). Once targeted to a specialized domain of the membrane, ion channels are stabilized by anchoring partners/associate subunits to be functional (green). Then, signals for internalization (blue arrows) lead to either degradation or recycling. PM, plasma membrane; EE, early endosome; LE, late endosome; ECM, extracellular matrix; RE, recycling endosome; GC, Golgi complex; ER, endoplasmic reticulum; SV, secretory vesicle.