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1 Istituto Pasteur Fondazione Cenci-Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Università di Roma ‘La Sapienza’, P.le Aldo Moro 5, I-00185 Roma, Italy
2 Fondazione Santa Lucia, Via Ardeatina, Roma, Italy
Ca2+ entry through neuronal nicotinic ACh receptors (nAChRs) modulates many biological processes in nervous tissue. In order to study the functional role of nAChRs in peripheral sensory signalling, we measured their Ca2+ permeability in rat dorsal root ganglion (DRG) neurones, and analysed the effects of nAChR-mediated Ca2+ influx on the function of the vanilloid receptor TRPV1. The fractional Ca2+ current (Pf, i.e. the percentage of current carried by Ca2+ ions) flowing through nAChR channels was measured by Ca2+ imaging fluorescence microscopy in combination with the patch-clamp technique. Functional nAChRs were expressed in a subset of adult DRG neurones (about 24% of the cells), typically with small to medium size as measured by their capacitance (40 ± 3 pF). In most cells, ACh evoked slowly desensitizing currents, insensitive to methyllycaconitine (MLA, 10 nM), a potent antagonist of homomeric nAChRs. Fast decaying currents, probably mediated by 
7*-nAChRs (i.e. native 7-containing nAChRs), were observed in 15% of ACh-responsive cells, in which slowly decaying currents, mediated by heteromeric nAChRs, were simultaneously present. The nAChRs of adult DRG neurones exhibited a Pf value of 2.2 ± 0.6% in the presence of MLA and 1.9 ± 0.6% (P > 0.1) in the absence of MLA, indicating that homomeric MLA-sensitive nAChRs do not contribute to Ca2+ entry into adult DRG neurones. Conversely, 10% of neonatal DRG neurones showed ACh-evoked currents completely blocked by MLA. In these neurones, nAChRs showed a larger Pf value (9.5 ± 1.5%), indicating the expression of bona fide 7*-nAChRs. Finally, we report that Ca2+ influx through nAChRs in adult DRG neurones negatively modulated the TRPV1-mediated responses, representing a possible mechanism underlying the analgesic properties of nicotinic agonists on sensory neurones.
(Received 10 February 2005;
accepted after revision 7 March 2005;
first published online 10 March 2005)
Corresponding author S. Fucile: Dipartimento di Fisiologia Umana e Farmacologia, P.le Aldo Moro 5, I-00185 Roma, Italy. Email: sergio.fucile{at}uniroma1.it
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