Commentary: Ion Channels, Fusion Pores and Exocytosis

Abstract

The key function of adrenal chromaffin cells is to secrete catecholamines in response to stress. Under stress, chromaffin cells are stimulated by cholinergic synaptic inputs resulting in catecholamine release. This stimulus-secretion coupling is mediated by activation of Ca signaling through ion channels followed by fusion pore formation and exocytosis, and subsequent endocytosis. Several sessions at this symposium highlighted advances in the understanding of the role of ion channels in exocytosis and endocytosis, the mechanics of fusion pore formation and the role of Ca syntillas and gap junctional communication in modulating catecholamine release. As well, new technologies used to investigate stimulus–secretion coupling in catecholamine release were presented. The functions of different types of calcium channels in exocytosis and endocytosis, as well as other ion channels in chromaffin cell function were discussed in two sessions: “Voltage-gated calcium channels and cell function” organized by Emilio Carbone (Italy) and “Structure and function of channels” organized by Jiu-Ping Ding (China). Among the speakers discussing the role of calcium channels in exocytosis/endocytosis were Luis Gandia (Spain) who gave an update on the role L-type Ca channels (LTCCs; Cav1) play in the control of Ca-dependent endocytosis. Gandia’s group brought new evidence that endocytosis in bovine chromaffin cells is likely associated with prolonged Ca entry during cell depolarization and is likely associated with slowly inactivating Ca channels rather than due to a colocalization of LTCCs with the clathrin-mediated endocytotic machinery. Indeed, immunostaining of L-, P/Q, and Ntype channels showed no colocalization with clathrin, and application of roscovitine (a blocker of N and P/Q type channel inactivation) restored endocytosis when LTTCs were blocked by nifedipine. Thus, “compensatory” and “excess” endocytosis is driven by the Ca entry through slowly inactivating Ca channels. More extensive discussions on the role of different calcium channel subtypes on endocytosis in chromaffin cells is presented in a review by Luis Gandia below. Antonio Miguel G. de Diego (Spain) reviewed the possibility that LTCCs could exert control on exocytosis induced by acute hypoxia in rat embryo chromaffin cells. According to this, LTCCs (besides T-type channels) are also likely to be involved in the control of catecholamine release at the embryonic stage, when chromaffin cells are particularly sensitive to O2 homeostasis and control cardiovascular responses. Emilio Carbone gave an overview of the ion channels controlling the spontaneous pacemaking of E. Carbone Department of Neuroscience, NIS Center, National Institute of Neuroscience, University of Torino, 10125 Torino, Italy