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

Abstract

Expression, spatial distribution and speciWc roles of diVerent Ca 2+ channels in stimulus-secretion coupling of chromaYn cells are intriguing issues still open to discussion. Most of the evidence supports a role of high-voltage activated (HVA) Ca 2+ channels (L-, N-, P/Q-and R-types) in the control of exocytosis: some suggesting a preferential coupling of speciWc Ca 2+ channel subunits with the secretory apparatus, others favoring the idea of a contribution to secretion proportional to the expression density and gating properties of Ca 2+ channels. In this work we review recent Wndings and bring new evidence in favor of the hypothesis that also the LVA (low-voltage-activated, T-type) Ca 2+ channels eVectively control fast exocytosis near resting potential in adrenal chromaYn cells of adult rats. Ttype channels recruited after long-term treatments with pCPT-cAMP (or chronic hypoxia) are shown to control exocytosis with the same eYcacy of L-type channels, which are the dominant Ca 2+ channel types expressed in rodent chromaYn cells. A rigorous comparison of T-and L-type channel properties shows that, although operating at diVerent potentials and with diVerent voltage-sensitivity, the two channels possess otherwise similar Ca 2+ -dependence of exocytosis, size and kinetics of depletion of the immediately releasable pool and mobilize vesicles of the same quantal size. Thus, T-and L-type channels are coupled with the same Ca 2+ -eYciency to the secretory apparatus and deplete the same number of vesicles ready for release.The major diVerence of the secretory signals controlled by the two channels appear to be the voltage range of operation, suggesting the idea that stressful conditions (hypoxia and persistent -adrenergic stimulation) can lower the threshold of cell excitability by recruiting new Ca 2+ channels and activate an additional source of catecholamine secretion.

Pituitary Adenylate Cyclase-activating Peptide (PACAP) Recruits Low Voltage-activated T-type Calcium Influx under Acute Sympathetic Stimulation in Mouse Adrenal Chromaffin Cells

“…R-type channels are HVA calcium channels sensitive to nickel block with an initial activation potential of Ϫ40 mV (39). We selected a concentration of nickel chloride optimal for blocking T-type channels in chromaffin cells (43,58); however, the positive activation potential of the Ni 2ϩ -sensitive current presented in Fig. 2 indicates a component of R-type current in our Ni 2ϩ subtraction data.…”

CaV1.3 as pacemaker channels in adrenal chromaffin cells: Specific role on exo- and endocytosis?

“…First, Ca V 1.2 and Ca V 1.3 channels markedly contribute to catecholamine secretion. [12][13][14][15] In rat (RCCs) and mouse chromaffin cells (MCCs) they are responsible for nearly half of the total Ca 2+ current and the corresponding exocytosis. 12,[16][17][18][19][20] Second, compensatory and excess endocytosis are strongly attenuated when LTCCs are blocked.…”

“…For instance, Ca V 2.1 deletion causes a loss of the P/Q-type currents with a compensatory increase of L-type currents and secretion. 69 Similarly, when upregulated by cAMP 14 or chronic hypoxia, 70 T-type channels contribute to low-threshold exocytosis with the same Ca 2+ -dependence of L-type channels. In RCCs and MCCs, LTTCs represent the final target of different modulatory pathways mediated by the activation of either ).…”

L-type calcium channels in adrenal chromaffin cells: Role in pace-making and secretion

“…A rigorous comparison of T-and L-type channel properties shows that, although operating at different potentials and with different voltage-sensitivity, the two channels possess otherwise similar Ca 2+ -dependence of exocytosis, size of the immediately releasable pool and mobilize vesicles of the same quantal size. Thus, T-and L-type channels are coupled with the same Ca 2+ -efficiency to the secretory apparatus and deplete the immediately releasable pool with the same rate of release [92,93].…”