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

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