Chemosensitivity of medullary inspiratory neurones: a role for GABA(A) receptors?

Abstract

This study tested the hypothesis that during hypercapnia partial removal of a tonic GABA-mediated inhibition contributes to the increase in activity of the ventrolateral medulla (VLM) inspiratory neurones. Extracellular recordings were taken from 22 inspiratory neurones in the VLM of rats anaesthetised with pentobarbitone and artificially ventilated. It was found that during hypercapnia, changes in the discharge pattern (i.e. an increase in the discharge frequency during the neurone's normally active phase) and firing frequency of the VLM inspiratory neurones were similar to those evoked by GABA(A) receptor antagonist bicuculline methiodide (BMI, 10 mM, 20 nA), applied ionophoretically in conditions of normocapnia. During hypercapnia BMI (20 nA) failed to evoke a further increase in firing of these neurones. This suggests that CO2-evoked activation of VLM inspiratory neurones may involve a withdrawal in part of a tonic GABA(A) receptor-mediated inhibition. This disinhibition may play a role in the hypercapnia-induced increase in ventilatory activity.