Opposing roles of K+and Cl−channels in maintenance of opossum lower esophageal sphincter tone

Abstract

The ionic basis underlying the maintenance of myogenic tone of lower esophageal sphincter circular muscle (LES) was investigated in opossum with the use of standard isometric tension and conventional intracellular microelectrode recordings in vitro. In tension recording studies, nifedipine (1 μM) reduced basal tone to 27.7 ± 3.8% of control. The K+channel blockers tetraethylammonium (TEA, 2 mM), charybdotoxin (100 nM), and 4-aminopyridine (4-AP, 2 mM) enhanced resting tone, whereas apamin and glibenclamide were without affect. Cl−channel blockers DIDS (500 μM) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (500 μM), as well as niflumic acid (0.1–300 μM), decreased basal tone, but tamoxifen was without effect. Intracellular microelectrode recordings revealed ongoing, spontaneous, spike-like action potentials (APs). Nifedipine abolished APs and depolarized resting membrane potential (RMP). Both TEA and 4-AP significantly depolarized RMP and augmented APs, whereas niflumic acid dose-dependently hyperpolarized RMP and abolished APs. These data suggest that, in the opossum, basal tone is associated with continuous APs and that K+and Ca2+-activated Cl−channels have important opposing roles in the genesis of LES tone.