Muscarinic Regulation of Ca2+ Currents in Rat Sensory Neurons: Channel and Receptor Types, Dose ‐ response Relationships and Cross‐talk Pathways

Enzo Wanke, Laura Bianchi, Massimo Mantegazza, Ezia Guatteo, Enzo Mancinelli, Arnaldo Ferroni

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Abstract

We studied, in rat sensory neurons, the modulation of high voltage-activated Ca2+ currents (I(Ca)) mediated by the pertussis toxin-sensitive activation of muscarinic receptors, which were found to be of subtypes M2 or M4. Muscarine reversibly blocked somatic Ca2+ spikes but strong predepolarizations only partially relieved the inhibited Ca2+ current. On the other hand, the putative coupling messenger could not rapidly diffuse towards channels whose activity was recorded from a macro-patch. The perforated patch technique virtually prevented the response rundown present during whole-cell experiments. Both ω-conotoxin GVIA (ω-CgTx)-sensitive channels and ω-CgTx- and dihydropyridine-resistant channels are coupled to the muscarinic receptor, but not the L-channel. When measured in the same neuron, dose- response relationships for the first and subsequent agonist applications differed; maximal inhibition, the reciprocal of half-maximal concentration and the Hill coefficient were always highest in the first trial. Muscarine and oxotremorine exhibited monotone dose-response curves, but oxotremorine-M showed non-linear relationships which became monotonic when cells were intracellularly perfused with inhibitors of protein kinase A (PKA) and C (PKC), suggesting that either PKA or receptor-induced PKC could phosphorylate and thus inactivate G-proteins or other unknown proteins involved in inhibitory muscarinic actions on I(Ca). In summary, these data provide a preliminary pharmacological characterization of the muscarinic inhibition of the Ca2+ channels in sensory neurons, with implications about agonist specificity and the interplay between signalling pathways.

Original languageEnglish (US)
Pages (from-to)381-391
Number of pages11
JournalEuropean Journal of Neuroscience
Volume6
Issue number3
DOIs
StatePublished - Mar 1994

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Keywords

  • Ca channels
  • Muscarine receptor
  • Sensory neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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