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Department of Neuroscience, INFM Research Unit, 10125 Torino, Italy

T-type channels are expressed weakly or not at all in adult rat chromaffin cells (RCCs) and there is contrasting evidence as to whether they play a functional role in catecholamine secretion. Here we show that 3–5 days after application of pCPT-cAMP, most RCCs grown in serum-free medium expressed a high density of low-voltage-activated T-type channels without altering the expression and characteristics of high-voltage-activated channels. The density of cAMP-recruited T-type channels increased with time and displayed the typical biophysical and pharmacological properties of low-voltage-activated Ca²⁺ channels: (1) steep voltage-dependent activation from –50 mV in 10 mM Ca²⁺, (2) slow deactivation but fast and complete inactivation, (3) full inactivation following short conditioning prepulses to –30 mV, (4) effective block of Ca²⁺ influx with 50 µM Ni²⁺, (5) comparable permeability to Ca²⁺ and Ba²⁺, and (6) insensitivity to common Ca²⁺ channel antagonists. The action of exogenous pCPT-cAMP (200 µM) was prevented by the protein synthesis inhibitor anisomycin and mimicked in most cells by exposure to forskolin and 1-methyl-3-isobutylxanthine (IBMX) or isoprenaline. The protein kinase A (PKA) inhibitor H89 (0.3 µM) and the competitive antagonist of cAMP binding to PKA, Rp-cAMPS, had weak or no effect on the action of pCPT-cAMP. In line with this, the selective Epac agonist 8CPT-2Me-cAMP nicely mimicked the action of pCPT-cAMP and isoprenaline, suggesting the existence of a dominant Epac-dependent recruitment of T-type channels in RCCs that may originate from the activation of ß-adrenoceptors. Stimulation of ß-adrenoceptors occurs autocrinally in RCCs and thus, the neosynthesis of low-voltage-activated channels may represent a new form of ‘chromaffin cell plasticity’, which contributes, by lowering the threshold of action potential firing, to increasing cell excitability and secretory activity during sustained sympathetic stimulation and/or increased catecholamine circulation.

(Received 15 January 2004; accepted after revision 6 May 2004; first published online 14 May 2004)
Corresponding author E. Carbone: Department of Neuroscience, INFM Research Unit, 10125 Torino, Italy. Email: emilio.carbone{at}unito.it

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