Ionic mechanism of substance P actions on neurons in trigeminal root ganglia.
1. Responses of primary sensory neurons to substance P applications by perfusion were studied with intracellular recording techniques in in vitro slice preparations of trigeminal root ganglia (guinea pigs). Application of substance P in micromolar doses produced reversible depolarizations of 2-47 mV in 48 out of 64 neurons. The depolarizing influence facilitated repetitive spike discharge evoked by current-pulse injection. Evidence of desensitization was observed during prolonged or repeated applications of the peptide. 2. The responses to substance P were associated with decreased input resistance, although increased input resistance was observed in neurons where the resting membrane potential was compensated with DC injection. In single-electrode voltage-clamp (SEVC) recordings, substance P evoked an inward shift in the holding current and reduced an outwardly rectifying component in the I-V relationships. The reversal potential for the substance P response could not be determined. These results suggested that the perikaryal response to substance P has a complex ionic mechanism involving activation and deactivation of membrane conductances. 3. Substance P-induced depolarizations were greatly attenuated during perfusion with solutions that were deficient in [Na+] or [Mg2+] and were not significantly affected during perfusion with low-[Ca2+]-, CO2(+)-containing solutions. 4. In the voltage-clamp investigations, an inward current contributed to the substance P responses during combined application with the K(+)-channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). This current was not abolished by the inclusion of CsCl in the perfusing solution or by internal Cs+ application from the recording electrode, suggesting that an anomalous inward rectifier was not involved in the responses to substance P.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
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Spigelman
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Puil
D000200:Action Potentials / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D012964:Sodium / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D013373:Substance P; D012964:Sodium; D002118:Calcium