Noncholinergic membrane potential responses to transmural nerve stimulation in the guinea pig ileum.

We sought to characterize the projections of nonmuscarinic intramural inhibitory and excitatory neural input to the circular muscle layer of the small intestine. Intracellular membrane potential recordings were made in smooth muscle cells from the distal ileum of 22 guinea pigs. Intramural nerve stimulation (4 pulses, 15 mA, 20 Hz, 2 ms) was delivered by two electrodes located at varying distances from the recording electrode along the longitudinal axis of the intestine. The membrane potential responses immediately oral to the stimulus consisted of an abrupt-onset inhibitory junction potential (IJP) followed by two distinct depolarizations, an early excitatory junction potential (EJP) and a late EJP. The early IJP and early and late EJPs were observed as far as 53 +/- 5, 56 +/- 6, and 39 +/- 5 mm oral to the stimulus, respectively. The responses immediately anal to the stimulus consisted of an initial IJP followed by a prolonged hyperpolarization, which was sometimes interrupted by a superimposed EJP. The early IJP, EJP, and late IJP were observed as far as 77 +/- 12, 66 +/- 10, and 37 +/- 13 mm anal to the stimulus, respectively. All excitatory events greater than 5-10 mm oral or anal to the stimulus were blocked by hexamethonium. Hexamethonium slightly antagonized the early IJP oral to the stimulus but had no effect on the early IJP anal to the stimulus. The late IJP was not affected by hexamethonium. These studies are the first to describe a late IJP, which is observed only at sites anal to the stimulus, and a late EJP, which is observed only at sites oral to the stimulus. The neural pathways involved in these late synaptic events (late EJP and IJP) as well as the previously described early synaptic events (early EJP and IJP) are discussed.