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

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.

Intracellular Liposomes and Cholesterol Deposits in Chronic Cholecystitis and Biliary Sludge

“…Initially described in hepatocytes [32], the mere presence of these organelles in the cholecystocytes islikelyindicative of excessive sterols and cholesterol intake either due to a high level of circulating lipids and=or the inflammatory processes. This exaggerated intake could alter the homeostatic functions of their membranes because an excessive intake in the smooth muscles of the gallbladder wall alters their membrane potentials [33]. In chronic cholecystitis, the epithelial intake of cholesterol and many other lipids have been demonstrated [3,4,11,16].…”

Characterization of methyl-β-cyclodextrin toxicity in NGF-differentiated PC12 cell death

“…MβCD depletes selectively cholesterol from the plasma membrane (Kilsdonk et al, 1995;Christian et al, 1997;Ilangumarn and Hoessli, 1998) and cholesterol-CDs complexes have been shown to increase the cellular content of cholesterol (Bernard et al, 1990;Christian et al, 1997;Racchi et al, 1997;Jennings et al, 1999). Depletion of plasma membrane cholesterol with MβCD is usually accomplished by incubations for short (∼1 h) periods with high (∼1-2%) concentrations of MβCD (Ilangumaran and Hoessli, 1998;Abrami et al, 1999).…”

Cholesterol Regulates Volume-Sensitive Osmolyte Efflux from Human SH-SY5Y Neuroblastoma Cells following Receptor Activation

“…Cholesterol availability has been reported to modulate the activity of several different ion channels (Bolotina et al, 1989;Jennings et al, 1999;Martens et al, 2001;Lockwich et al, 2000), in addition to that of VSOAC. In agreement with previous studies of non-neural cells, depletion of cholesterol from SH-SY5Y cells by pretreatment with CD under relatively mild conditions (5 mM for 10 min) facilitated the basal release of taurine in response to hypotonicity.…”