MEMBRANE POTENTIAL CHANGES INDUCED BY 5‐HYDROXYTRYPTAMINE IN THE RABBIT SUPERIOR CERVICAL GANGLION

Abstract

1 Changes in resting membrane potential induced by 5-hydroxytryptamine (5-HT) have been measured in the excised ganglion by the sucrose-gap technique. 2 5-HT produced a rapid depolarization, the threshold concentration for depolarization being around 10 μM. With concentrations of 100 μM or greater, repolarization began during the course of the supervision; this was followed by prolonged tachyphylaxis. 3 Tachyphylaxis was largely avoided by making injections into the superfusion stream. Standard injections of 0.2 μmol 5-HT dissolved in 0.2 ml of Krebs solution were used routinely and could be given at 20–30 min intervals to evoke relatively constant responses. 4 The response to an injection consisted of a rapid depolarization, followed by a rapid repolarization and subsequent after-hyperpolarization. The threshold quantity for depolarization was around 0.01 μmol, while the ED₅₀ estimated from 6 dose-response curves was 0.12 ± 0.02 μmol (mean ± s.e. mean). 5 Injections of 5-HT (0.2 μmol), choline (10 μmol) and acetylcholine (9.9 μmol) produced depolarizations of similar magnitude. 6 Monoamine oxidase inhibitors failed to alter substantially the amplitude of depolarizations to 5-HT. 7 5-HT depolarizations were unaltered in amplitude when the impermeant anion benzenesulphonate was substituted for the chloride ion in Krebs solution, but were initially markedly reduced in amplitude in a sodium-deficient medium; some recovery of the response subsequently occurred. The depolarization which persisted in sodium-deficient solutions was much reduced or abolished when calcium ions were then removed from the superfusion medium. Removal of either calcium ions alone or potassium ions from the superfusion fluid did not reduce depolarization amplitude. 8 The after-hyperpolarization was abolished in sodium-deficient solutions, usually increased in potassium-free solutions, reduced or abolished by ouabain or nicotine, but unaffected by calcium-free solutions. 9 A depolarizing action of 5-HT on presynaptic terminals in the ganglion appears probable.