Disinhibition during myoelectric complexes in the mouse colon.

Intracellular microelectrodes were used to record electrically evoked inhibitory junction potentials (IJPs) and electrotonic potentials during spontaneous cyclical depolarisations (myoelectric complexes, MCs) in the circular muscle layer of mouse colon in vitro. In the presence of nifedipine (1-2 microM) and atropine (1 microM), MCs were recorded every 264 +/- 18 s. Between MCs, single electrical stimuli (15 V, 0.6 ms, every 8 s) elicited IJPs whose amplitudes remained constant. In comparison, during the depolarising phase of MCs, the mean IJP amplitude was reduced by 61 +/- 7%, while during the late plateau and early repolarising phase of MCs, IJP amplitude was increased (up to 20%). NG-nitro-L-arginine (NOLA, 100 microM) abolished the repolarisation phase between MCs, so that the circular muscle remained depolarised and the amplitude of MCs was reduced by 73 +/- 6%. However, the amplitude of evoked IJPs was unaffected, as was the decrease in their amplitude during the depolarising phase of the residual MCs. In the presence of NOLA (100 microM), the further addition of apamin (250 nM) reduced the amplitude of evoked IJPs by approximately half. However, the amplitudes of NOLA- and apamin-resistant IJPs were also attenuated by 82 +/- 5% during the depolarising phase of residual MCs (amplitude: 1.9 +/- 1 mV). However, during this phase, the amplitude of an electrotonic potential (evoked by extracellular current application) was not attenuated. Addition of hexamethonium (500 microM), or tetrodotoxin (TTX) (1.6 microM) to solutions containing NOLA and apamin were without effect on membrane potential, but the residual MCs and the cyclical attenuation in IJP amplitude were abolished. During the intervals between MCs, membrane potential is maintained under tonic inhibition, via spontaneous release of inhibitory neurotransmitter(s), predominantly through nitrergic mechanisms. The cyclical attenuation in the amplitude of the non-nitrergic IJP does not arise from cyclical postjunctional changes in membrane resistance or potential. Moreover, the generation of the depolarising phase of MCs involves the simultaneous suppression of both nitrergic and non-nitrergic inhibitory neurotransmission. It is suggested that MCs arise from presynaptic suppression of ongoing inhibitory neurotransmitter release.