Effects of protons on muscarinic receptor cationic current in
single visceral smooth muscle cells.
Zholos, Alexander V., and Thomas B. Bolton.
Department of Pharmacology & Clinical Pharmacology, St. George's
Hospital Medical School, London SW17 ORE
APStracts 3:0173G, 1996.
Effects of extracellular protons on muscarinic receptor cationic
current (Icat) in single guinea-pig ileal smooth muscle cells were
studied using patch-clamp techniques; pHi and pCai were buffered to
7.4 and 7.0 respectively, symmetrical 124 mM Cs+ solutions were used
and divalent cations were removed from the bathing solution.
Increasing pHo from 7.4 to 8.4 caused a 16 mV parallel negative shift
of the activation curve for Icat evoked by GTP-[tau]S with an
increase in the maximal conductance and slowed Icat relaxation upon
hyperpolarization; acidification to pHo 6.4 produced equivalent but
opposite effects. Carbachol- and GTP-[gamma]S-activated Icat behaved
similarly suggesting that the cationic channel rather than muscarinic
receptor was the major site of action. Progressively from pHo 11.4 to
pHo 4.4 maximal cationic conductance was reduced and the activation
curve shifted positively. Sodium, potassium, calcium and magnesium
ions had complex interactions with pHo-induced effects considered to
be attributable to interaction of protons with fixed negative surface
charges and, at positive potentials, to channel block.
Received 24 May 1996; accepted in final form 28 August 1996.
APS Manuscript Number G208-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996