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,wemeasuredtheirCa2+ permeability inrat dorsal rootganglion(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 α7∗-nAChRs (i.e. native α7-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 byMLA. In these neurones,nAChRs showed a larger Pf value (9.5±1.5%), indicating the expression of bona fide α7∗-nAChRs. Finally, we report that Ca2+ influx through nAChRs in adultDRGneurones negativelymodulated the TRPV1-mediated responses, representing a possible mechanism underlying the analgesic properties of nicotinic agonists on sensory neurones.
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|Titolo:||Ca2+ permeability of nicotinic acetylcholine receptors from rat dorsal root ganglion neurones|
|Data di pubblicazione:||2005|
|Appartiene alla tipologia:||01a Articolo in rivista|