CaV1.3 as pacemaker channels in adrenal chromaffin cells

Voltage-gated L-type calcium channels (LTCCs) are expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), LTCCs are involved in the excitation-secretion coupling controlling catecholamine release and in Ca2+-dependent vesicle retrieval. Of the two LTCCs expressed in chromaffin cells (Ca(V)1.2 and Ca(V)1.3), Ca(V)1.3 possesses the prerequisites for pacemaking spontaneously firing cells: low-threshold, steep voltage-dependence of activation and slow inactivation. By using Ca(V)1.3(-/-)KO mice and the AP-clamp it has been possible to resolve the time course of Ca(V)1.3 pacemaker currents, which is similar to that regulating Substantia nigra dopaminergic neurons. In mouse chromaffin cells Ca(V)1.3 is coupled to fast-inactivating BK channels within membrane nanodomains and controls AP repolarization. The ability to carry subthreshold Ca2+ currents and activate BK channels confers to Ca(V)1.3 the unique feature of driving Ca2+ loading during long interspike intervals and, possibly, to control the Ca2+-dependent exocytosis and endocytosis processes that regulate catecholamine secretion and vesicle recycling.