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

Expression, spatial distribution and speciWc roles of diVerent Ca2+ 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) Ca2+ channels (L-, N-, P/Q- and R-types) in the control of exocytosis: some suggesting a preferential coupling of speciWc Ca2+ channel subunits with the secretory apparatus, others favoring the idea of a contribution to secretion proportional to the expression density and gating properties of Ca2+ 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) Ca2+ 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 Ca2+ 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 Ca2+-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 Ca2+-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 Ca2+ channels and activate an additional source of catecholamine secretion.