Muscarinic regulation of Ca2+ currents in rat sensory neurons: Channel and receptor types, dose-response relationships and cross-talk pathways

E. Wanke, L. Bianchi, M. Mantegazza, E. Guatteo, E. Mancinelli, A. Ferroni

Research output: Contribution to journalArticle

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
Pages (from-to)381-391
Number of pages11
JournalEuropean Journal of Neuroscience
Volume6
Issue number3
Publication statusPublished - 1994

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Muscarine
Muscarinic Receptors
Sensory Receptor Cells
Cyclic AMP-Dependent Protein Kinases
Cholinergic Agents
Conotoxins
Oxotremorine
Pertussis Toxin
GTP-Binding Proteins
Protein Kinase C
Pharmacology
Neurons
Proteins
1,4-dihydropyridine
oxotremorine M

Keywords

  • Ca channels
  • Muscarine receptor
  • Sensory neuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Muscarinic regulation of Ca2+ currents in rat sensory neurons : Channel and receptor types, dose-response relationships and cross-talk pathways. / Wanke, E.; Bianchi, L.; Mantegazza, M.; Guatteo, E.; Mancinelli, E.; Ferroni, A.

In: European Journal of Neuroscience, Vol. 6, No. 3, 1994, p. 381-391.

Research output: Contribution to journalArticle

Wanke, E. ; Bianchi, L. ; Mantegazza, M. ; Guatteo, E. ; Mancinelli, E. ; Ferroni, A. / Muscarinic regulation of Ca2+ currents in rat sensory neurons : Channel and receptor types, dose-response relationships and cross-talk pathways. In: European Journal of Neuroscience. 1994 ; Vol. 6, No. 3. pp. 381-391.
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