On the mechanism of action of GABA in pelvic vesical ganglia: biphasic responses evoked by two opposing actions on membrane conductance.

Intracellular recording techniques were used to study the response of cat vesical pelvic ganglion neurones loaded with permeable anions to the application of GABA in vitro. In 106/127 neurones GABA evoked a biphasic response, the initial phase of which was depolarizing and associated with a conductance increase; the latter phase was hyperpolarizing and associated with a conductance decrease. The GABA evoked hyperpolarization and conductance decrease were related and behaved as though generated by closure of ion channels open in the resting membrane. The hyperpolarization had a strong inhibitory action on both spontaneous activity, and excitation evoked by depolarizing current injection and pre-synaptic nerve stimulation. Ion substitution experiments suggest that the conductance decrease is primarily to chloride ions, although other ionic species may contribute. Short iontophoretic applications of GABA-evoked monophasic depolarizing excitatory responses, even during the hyperpolarizing response evoked by perfusion of GABA, suggesting no cross-desensitization between the mechanisms generating the initial and late phases of the biphasic response.