Excitation of locus coeruleus neurons by vasoactive intestinal peptide: evidence for a G-protein-mediated inward current

Abstract

Vasoactive intestinal polypeptide (VIP) caused a reversible increase in the firing rate of locus coeruleus (LC) neurons. Voltage-clamp at −60 mV revealed that VIP induced an inward current, associated with a small increase in conductance. The inward current persisted in the presence of Co²⁺ (to block Ca²⁺ channels) or tetrodotoxin (to block fast voltage-dependent Na⁺ channels). Substitution (80%) of Na⁺ with choline or Tris reduced the VIP-elicited inward current by approximately 75%. Changing external K⁺ concentrations did not alter the effect of VIP. The inward current induced by VIP became irreversible after the intracellular administration of GTPγS, a hydrolysis-resistant analog of GTP which can cause a prolonged activation of G-proteins. The intracellular application of GDPβS, which can interfere with G-protein activation, attenuated the effect of VIP. Pertussis toxin, an inactivator of certain G-proteins, did not block the effect of VIP. We conclude that VIP directly excites LC neurons by inducing a largely Na-dependent inward current. As this effect became irreversible in the presence of intracellular GTPγS, was attenuated by GDPβS, and was not eliminated by pertussis toxin, mediation through a pertussis toxin-insensitive G-protein is suggested.