Evidence for non-cholinergic, non-adrenergic transmission in the guinea-pig ileum

Abstract

To elucidate further the innervation of the longitudinal and circular muscle cells of the guinea-pig ileum, junction potentials elicited by field stimulation were recorded from both muscle layers in the presence and absence of atropine (1-2 muM) with guanethidine (10 muM) at 36 degrees C.1. In longitudinal muscle cells, a single stimulus elicited an atropine-sensitive transient depolarization (cholinergic e.j.p.), whereas in circular muscle cells, a transient hyperpolarization (non-cholinergic non-adrenergic i.j.p.) was elicited. With stimulation of nerves in the presence of atropine and guanethidine, responses of circular muscle cells to nerve stimulation were preserved while the longitudinal muscle cells generated depolarization (non-ch., non-adr. e.j.p.), hyperpolarization (non-ch., non-adr. i.j.p.) or both depolarization and subsequent hyperpolarization. These potential changes ceased with application of TTX or excess Mg(2+).2. The latency for junction potentials recorded from longitudinal muscles after field stimulation was in the following order; non-ch., non-adr. e.j.p. < cholinergic e.j.p. < non-ch., non-adr. i.j.p. The cholinergic e.j.p.s had a lower, and non-ch., non-adr. i.j.p.s a higher threshold.3. At low frequencies of stimulation (below 1 Hz) amplitudes of successively generated cholinergic e.j.p.s and non-ch., non-adr. i.j.p.s were gradually reduced, but at higher frequencies (2-20 Hz) of stimulation they were summated. The amplitudes of non-ch., non-adr. e.j.p.s were, however, not affected at low frequencies of stimulation (up to 0.5 Hz) and were summated at higher frequencies (over 1 Hz) of stimulation.4. Reversal potentials for non-ch., non-adr. e.j.p.s and i.j.p.s estimated from the amplitude of junction potentials and membrane potential were -27 and -80 mV, respectively. The reversal potential for non-ch., non-adr. e.j.p.s was higher (more negative) than that for cholinergic e.j.p.s5. Generation of i.j.p.s in longitudinal muscle cells elicited by repetitive stimulation was followed by a rebound depolarization on which was superimposed a burst of spikes. During repetitive stimulation, the amplitude of hyperpolarization was gradually reduced but the rebound depolarization and spike discharge were enhanced. Thus, while the rebound depolarization was related to the amplitude of the preceding hyperpolarization it was more related to the duration of the stimulation.6. Therefore longitudinal muscles of the guinea-pig ileum show evidence of having in addition to cholinergic and adrenergic innervation, both excitatory and inhibitory non-ch., non-adr. innervation. In the longitudinal muscle layer of the ileum, the non-ch., non-adr. excitatory fibres are more densely distributed in the terminal rather than in the proximal region, while in the case of non-ch., non-adr. inhibitory fibres, the distribution is reversed. Circular muscle cells are, however, homogenously innervated by non-ch., non-adr. inhibitory nerves.