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)
Spigelman
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
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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