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Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle.
Jennings L, Xu Q, Firth T, Nelson MT, Mawe G
American Journal of Physiology-Gastrointestinal and Liver Physiology. 1999;277( 5 Pt 1):G1017-26.
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Abstract
Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions.
Keyword(s)
Animals; Boron Compounds; Electric Conductivity; Electric Stimulation; Female; Fluorescent Dyes; Guinea Pigs; Male; Patch-Clamp Techniques; chemistry: Gallbladder; chemistry: Muscle, Smooth; drug effects: Action Potentials; metabolism: Calcium; metabolism: Potassium; pharmacology: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology: Antihypertensive Agents; pharmacology: Calcitonin Gene-Related Peptide; pharmacology: Calcium Channel Agonists; pharmacology: Cholesterol; pharmacology: Pinacidil; physiology: Calcium Channels; physiology: Gallbladder Emptying; physiology: Potassium Channels; physiopathology: Biliary Tract; physiopathology: Cholelithiasis; physiopathology: Cholestasis