Voltage-gated L-type Ca²⁺ channels are highly expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), L-type channels are involved in the excitation-secretion coupling controlling catecholamine release and in the Ca²⁺-dependent vesicle retrieval. Of the two L-type channels expressed in chromaffin cells (Ca_V1.2 and Ca_V1.3), Ca_V1.3 possesses the prerequisites for pacemaking spontaneously firing cells near resting (0.6 to 3 Hz at -50 mV): low-threshold, steep voltage-dependence of activation and slow inactivation. By using Ca_V1.3^-/- KO mice and the AP-clamp it has been possible to resolve the time course of Ca_V1.3 pacemaker currents that regulate the spontaneous firing of adrenal chromaffin cells [1]. In mouse chromaffin cells, Ca_V1.3 is selectively coupled to BK potassium channels within membrane nanodomains and controls both the firing frequency and the action potential repolarization phase [2]. The ability to carry subthreshold Ca²⁺ currents confers to Ca_V1.3 also the unique feature of driving Ca²⁺ loading during long interspikes intervals (0.5 to 1 s) which activate SK potassium channels (KCNN1-3), known to be responsible for the termination of burst firings and for setting the resting potential, despite a lack of coupling to Ca_V1 channels.

Ca_V1.2 and Ca_V1.3 do also control a large fraction of the Ca²⁺-dependent exocytosis [3] and fast endocytosis (compensatory and excess) that regulate catecholamine secretion and vesicle recycling. Recent data in support of this will be discussed.

Bibliography 

1 - Marcantoni A et al. 2010. J Neurosci 30:491

2 - Vandael DHF et al. 2010. Molec Neurobiol 42:185

3 - Carabelli V et al. 2003. Biophys J 85:1326