Origin of 5‐hydroxytryptamine‐induced hyperpolarization of the rat superior cervical ganglion and vagus nerve

Abstract

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 × 10⁻⁸-3 × 10⁻⁷ m) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 × 10⁻⁶-1 × 10⁻⁴ m) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 × 10⁻⁵ m), quipazine (1 × 10⁻⁶ m) or MDL 72222 (1 × 10⁻⁵ m). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l⁻¹. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 × 10⁻³ m) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 × 10⁻⁷-3 × 10⁻⁵ m) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 × 10⁻⁶ m or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 × 10⁻⁵ m) but were unaffected by spiperone (1 × 10⁻⁷ m). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not mediated through 5-HT₃ receptors and is unlikely to be a consequence of depolarization. In contrast, on the rat vagus nerve, the post-5-HT hyperpolarization observed in the present study had the characteristics expected of depolarization-dependent activation of a sodium ion pump.