Low-threshold exocytosis induced by cAMP-recruited CaV3.2 (1H) channels in rat chromaffin cells

¹ Department of Neuroscience, NIS Centre of Excellence, CNISM Research Unit, Torino, Italy
² Department of Neuroscience, Torino, Italy
³ Department of Experimental Medicine, Genova, Italy

^* To whom correspondence should be addressed. E-mail: emilio.carbone{at}unito.it.

Submitted on July 29, 2005
Revised on September 13, 2005
Accepted on 29 November 2005

	Abstract

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 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⁺ that 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 increased secretion down-stream 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.

Key Words: T-type channels, cAMP, capacitance increases, exocytosis, ready releasable pool

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