Blockade of Gi/o proteins modifies electrical activity of S-myenteric neurons from guinea-pig ileum.

We have investigated the effect of blockade of G(i/o) proteins on the electrical activity of S-myenteric neurons from guinea-pig ileum longitudinal muscle-myenteric plexus preparations. Intracellular recordings were made from either control or pertussis toxin (PTX) treated tissues. PTX is known to disrupt the function of G(i/o) proteins. Incubation with PTX (300 ng/ml) induced three main changes in the electrophysiological characteristics of S-neurons: (1) resting membrane potential was more depolarised; (2) fast excitatory postsynaptic potentials (EPSPs) were faster and narrower; and (3) spontaneous fast EPSPs and action potentials were more frequent. Amplitude of slow EPSPs was not modified. This general increase in excitability after blockade of G(i/o) proteins shares characteristics with the slow depolarisation induced by long-lasting trains of low-frequency electrical stimulation and could be mediated by similar mechanisms. Electrophysiological activity of S-myenteric neurons could be modulated by an inhibitory tone, which PTX could modify by either pre- or post-synaptic mechanisms, such as inhibition of the tonic release of inhibitory neurotransmitters and/or intracellular signal transduction involving PTX-sensitive G(i/o) proteins.