Ca_v1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells

Abstract

Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuron-like” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.

Novel synthetic sulfoglycolipid IG20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels

“…An alternative explanation is that in addition to shifting the fast‐inactivating Nav channels expressed by chromaffin cells (Nav1.3 and Nav1.7; Vandael et al . ,b), IG20 may activate some non‐inactivating Na + channel that may sustain resting V m and thus cause cell depolarization.…”

Regulation of L-type CaV1.3 channel activity and insulin secretion by the cGMP-PKG signaling pathway

“…By using a site-directed mutagenesis approach we have pinpointed the residues within the Ca V 1.3α 1 pore-forming subunit, which are modulated by the cGMP-PKG signaling pathway. Likewise, given the low-threshold of activation and slow rate of inactivation of Ca V 1.3 channels, they could carry sufficient inward current at subthreshold potentials to activate K + channels which contribute to determine the membrane resting potential, as well as the action potential shape and frequency during spontaneous firing or sustained depolarizations [39,40]. Therefore, the findings described here also suggest that PKG phosphorylation could play important roles in the regulation of numerous cellular processes.…”

Small-Conductance Ca 2+ -Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells

“…BK channel mRNA expression is detected in both human adrenal samples and NCI-H295 cell line 42 , and the expression of SK channels in human adrenal cortex was detected by the Human Gene 1.0 ST Array 13 . The relative importance of SK versus BK channel types in the regulation of aldosterone production from the human adrenal cortex in vivo is as yet unexplored, but precedence for coordinated regulation of catecholamine secretion by these channel types is found in electrically excitable cells of adrenal medulla 43 .…”