Effects of protons on muscarinic receptor cationic current in single visceral smooth muscle cells.
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.
Zholos
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AV
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
Bolton
T B
TB
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D004553:Electric Conductivity; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D011976:Receptors, Muscarinic / Q000502:physiology*; D014781:Viscera / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002412:Cations; D007477:Ions; D018721:Muscarinic Agonists; D011522:Protons; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol