Properties of inhibitory junctional transmission in smooth muscle of the guinea pig lower esophageal sphincter.

Inhibitory neurotransmission in guinea pig lower esophageal sphincter (LES) muscles was investigated by using electrophysiological methods. Transmural nerve stimulation (TNS) initiated an inhibitory junction potential (i.j.p.); the amplitude increased 35% by atropine (10(-6) M) and converted to a muscarinic excitatory junction potential (e.j.p.) by apamin (10(-7) M) plus Nomega-nitro-L-arginine (L-NNA, 10(-5) M). In atropinized tissue, the i.j.p. amplitude was reduced 58% by guanethidine (5 x 10(-6) M), 41% by L-NNA (10(-5) M), 57% by suramin (10(-4) M), and it was abolished by apamin (10(-7) M), suggesting that this potential was produced by ATP and nitric oxide (NO) released from adrenergic and nitrergic nerves, respectively, through the activation of Ca2+-sensitive K+ channels. Hyperpolarizations produced by ATP and NO were inhibited by apamin. The i.j.p. amplitude was reduced after desensitizing the membrane with ATP. In atropinized tissue, TNS produced a relaxation that was reduced 15% by guanethidine (5 x 10(-6) M), 50% by L-NNA (10(-5) M), and 30% by apamin (10(-7) M). Thus the LES receives cholinergic excitatory and adrenergic and nitrergic inhibitory innervations; the latter two components contribute evenly to the i.j.p. generation. The relaxation is mainly produced by NO in a membrane potential-independent way.