Cholesterol inhibits spontaneous action potentials and calcium currents inguinea pig gallbladder smooth muscle

Elevated cholesterol decreases agonist-induced contractility and enhances s tone formation in the gallbladder. The current study was conducted to deter mine if and how the electrical properties and ionic conductances of gallbla dder smooth muscle are altered by elevated cholesterol. Cholesterol was del ivered as a complex with cyclodextrin, and effects were evaluated with intr acellular recordings from intact gallbladder and whole cell patch-clamp rec ordings from isolated cells. Cholesterol significantly attenuated the spont aneous action potentials of intact tissue. Furthermore, calcium-dependent a ction potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyper polarizations induced by the ATP-sensitive potassium channel opener, pinaci dil, nor voltage-activated outward potassium currents were affected by chol esterol. Hyperpolarizations elicited by calcitonin gene-related peptide wer e reduced by cholesterol enrichment, indicating potential changes in recept or 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. I n addition, cholesterol enrichment may also modulate receptor ligand behavi or and/or second messenger interactions.