AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 2 215-G223, Copyright © 1997 by American Physiological Society
Effects of protons on muscarinic receptor cationic current in single visceral smooth muscle cells
A. V. Zholos and T. B. Bolton
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
Effects of extracellular protons on muscarinic receptor-evoked cationic
current (Icat) in single guinea pig ileal smooth muscle cells were studied
by use of patch-clamp techniques: intracellular pH and pCa 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
extracellular pH (pHo) from 7.4 to 8.4 caused a 16-mV parallel negative
shift of the activation curve for Icat evoked by guanosine
5'-O-(3-thiotriphosphate) (GTPgammaS) with an increase in the maximal
conductance and slowed Icat relaxation on hyperpolarization; acidification
to pHo 6.4 produced equivalent but opposite effects. Carbachol- and
GTPgammaS-activated Icat behaved similarly, suggesting that the cationic
channel rather than the muscarinic receptor was the major site of action.
From 11.4 to 4.4 pHo, maximal cationic conductance was reduced
progressively, and the activation curve shifted positively. Na+, K+, Ca2+,
and Mg2+ 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.
