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Low-Threshold Exocytosis Induced by cAMP-Recruited Ca_V3.2 (_1H) Channels in Rat Chromaffin Cells

Department of Neuroscience, NIS Centre of Excellence, CNISM Research Unit, 10125 Turin, Italy

Correspondence: Address reprint requests to Emilio Carbone, Dept. of Neuroscience, Corso Raffaello 30, 10125 Turin, Italy. Tel.: 39-011-670-7786; Fax: 39-011-670-7708; E-mail: emilio.carbone{at}unito.it.

We have studied the functional role of Ca_V3 channels in triggering fast exocytosis in rat chromaffin cells (RCCs). Ca_V3 T-type channels were selectively recruited by chronic exposures to cAMP (3 days) via an exchange protein directly activated by cAMP (Epac)-mediated pathway. Here we show that cAMP-treated cells had increased secretory responses, which could be evoked even at very low depolarizations (–50, –40 mV). Potentiation of exocytosis in cAMP-treated cells did not occur in the presence of 50 µM Ni²⁺, which selectively blocks T-type currents in RCCs. This suggests that the "low-threshold exocytosis" induced by cAMP is due to increased Ca²⁺ influx through cAMP-recruited T-type channels, rather than to an enhanced secretion downstream of Ca²⁺ entry, as previously reported for short-term cAMP treatments (20 min). Newly recruited T-type channels increase the fast secretory response at low voltages without altering the size of the immediately releasable pool. They also preserve the Ca²⁺ dependence of exocytosis, the initial speed of vesicle depletion, and the mean quantal size of single secretory events. All this indicates that cAMP-recruited Ca_V3 channels enhance the secretory activity of RCCs at low voltages by coupling to the secretory apparatus with a Ca²⁺ efficacy similar to that of already existing high-threshold Ca²⁺ channels. Finally, using RT-PCRs we found that the fast inactivating low-threshold Ca²⁺ current component recruited by cAMP is selectively associated to the _1H (Ca_V3.2) channel isoform.

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