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 mu scarinic excitatory junction potential (e.j.p.) by apamin (10(-7) M) plus N -omega-nitro-L-arginine (L-NNA, 10(-5) M), In atropinized tissue, the i.j.p . amplitude was reduced 58% by guanethidine (5x10(-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 a ctivation of Ca2+-sensitive K+ channels. Hyperpolarizations produced by ATP and NO were inhibited by apamin. The i.j.p. amplitude was reduced after de sensitizing the membrane with ATP. In atropinized tissue, TNS produced a re laxation that was reduced 15% by guanethidine (5x10(-6) M), 50% by L-NNA (1 0(-5) M), and 30% by apamin (10(-7) M). Thus the LES receives cholinergic e xcitatory and adrenergic and nitrergic inhibitory innervations; the latter two components contribute evenly to the i.j.p. generation. The relaxation i s mainly produced by NO in a membrane potential-independent way.