Three types of Ca2+ channel trigger secretion with different efficacies in chromaffin cells

Abstract

To determine whether the different types of Ca2+ channels present in the same secretory cell contribute equally to secretion, we used chromaffin cells to analyse the coupling between three distinct types of Ca2+ channel and exocytosis. These are omega-conotoxin-GVIA-sensitive N-type channels, omega-agatoxin-IVA-sensitive P-type Ca2+ channels and dihydropyridine-sensitive facilitation Ca2+ channels, which are normally quiescent but are activated by depolarizing pre-pulses, repetitive depolarizations to physiological potentials, or agents that raise cyclic AMP. We have simultaneously monitored changes in capacitance as an assay of catecholamine secretion, and Ca2+ currents. Although all three types of Ca2+ channel trigger secretion individually, facilitation channels produce much greater secretion for a given size of Ca2+ current, indicating that they are coupled more efficiently to exocytosis. These results indicate that facilitation Ca2+ channels may be physically nearer vesicle release sites. They also show that low efficiency P- and N-type channels could trigger mild release and that high-efficiency facilitation channels may underlie the massive catecholamine release that occurs during the 'fight or flight' response.

Protein kinase C activator inhibits voltage‐sensitive Ca2+ channels and catecholamine secretion in adrenal chromaffin cells

“…the dihydropyridine-sensitive L-type channel, the co-conotoxin GVIA-sensitive N-type channel and the FTX-and w-agatoxin IVa-sensitive P-type channel [15,16,21]. The Ca 2+ currents supported by these channels vary markedly from cell to cell [22], suggesting a highly heterogenous distribution of Ca > channels among chromaffin cells.…”

Short-Term Changes in the Ca2+-Exocytosis Relationship during Repetitive Pulse Protocols in Bovine Adrenal Chromaffin Cells

“…In all cells, the voltage-gated Ca 2ϩ current showed typical inactivation during a train (Fig. 2 B; comparison of first and last current), with no evidence for activation of additional "facilitation" channels as described for calf chromaffin cells (Artalejo et al, 1991(Artalejo et al, , 1994.…”

Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+-dependence

“…This slower exocytotic process is primarily controlled by Ca 2+ inXux through multiple isoforms of high-voltage activated Ca 2+ channels, which contribute to secretion proportionally to their density of expression and gating properties, with no speciWc requirements of Ca 2+ channels colocalization to the release sites (Kim et al 1995;Engisch and Nowycky 1996;Klingauf and Neher 1997;Lukyanetz and Neher 1999;Ulate et al 2000;Carabelli et al 2003;Chan et al 2005;Giancippoli et al 2006;Polo-Parada et al 2006). Alternatively, other groups suggest a preferential role of some channel subtype in close proximity to the secretory sites (Lopez et al 1994;Artalejo et al 1994;Lara et al 1998;O'Farrel and Marley 2000;Albillos et al 2000) and a further role of mitochondria in sequestering Ca 2+ entering through Ca 2+ channels (Ales et al 2005). In addition to this, the eYciency of stimulus-secretion coupling can be altered in many ways, some relevant examples are: (1) PKC activation, which enhances exocytosis (Gillis et al 1996), (2) rapid and sustained increase of intracellular cAMP, which potentiates Ltype channel densities and secretion at diVerent proportions , (3) transdiVerentiation of chromaYn cells with astrocyte-conditioned medium, which promotes the acquisition of a neuronal phenotype and accelerates the exocytotic kinetics, by a better coupling between secretory vesicles and Ca 2+ channels (Ardiles et al 2006) and (4) -adrenergic stimulation, which enhances the stimulus-secretion coupling of Ltype Ca 2+ channels by repeated action potential-like stimulations (Polo-Parada et al 2006).…”