The depolarizing action of 5-HT on mammalian non-myelinated nerve fibres

Abstract

The effects of 5-hydroxytryptamine (5-HT) on nerve fibres in the rabbit cervical vagus and on the sciatic nerve “in vitro” were studied by the single sucrose-gap technique. The addition of 5-HT to the Locke solution bathing the vagus nerve induced rapid depolarization and a fall in spike height at the threshold concentration of 1 × 10 −7 M. In most cases the depolarizing effect was completely reversed by washing for 5–10 min while in about 40% of the preparations the action potential amplitude remained 10–30% below the control level. These effects were dose-related up to a maximum concentration of 3 × 10 −5 M. Tachyphylaxis was not observed when the drug was added at 12–15 min intervals. Depolarization was abolished by perfusing the nerve with sodium-free medium or by previous exposure to lidocaine (10 −3). External hyperpolarizing currents (10 −7 to 10 −6A) were not able to restore the action potential amplitude. Cyproheptadine (50 μM), which was found to have a slight local anesthetic action, reduced the 5-HT-induced depolarization by 20–30%. Methysergide (50 μM), a more specific 5-HT antagonist, did not affect the action of 5-HT. 5-HT was inactive when applied to the myelinated fibres of the sciatic nerve. Our results indicate that 5-HT-induced depolarization appears to be related to an increase in the resting sodium permeability of nerve fibres.