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channels in maintenance of opossum
lower esophageal sphincter tone
Gastrointestinal Diseases Research Unit and Departments of Medicine and Physiology, Queen's University, Kingston, Ontario, Canada K7L 5G2
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.
smooth muscle; spontaneous action potentials; myogenic tone; niflumic acid; nifedipine.
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