Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity

Background & Aims: The relationship between muscle contractility, plasma me mbrane cholesterol, and fluidity was investigated in human gallbladders wit h gallstones. Methods: isolated gallbladder muscle cells were used to measu re contraction. Plasma membranes of gallbladder muscle were purified in a s ucrose gradient and measured for cholesterol content and cholesterol/phosph olipid mole ratio. Membrane fluidity was determined by using fluorescence p olarization and was expressed as the reciprocal of anisotropy. Results: The maximal contraction induced by cholecystokinin octapeptide was significant ly less in gallbladders with cholesterol stones than in those with pigment stones. The membrane cholesterol content and cholesterol/phospholipid mole ratio were significantly higher in gallbladders with cholesterol stones tha n in those with pigment stones. Membrane anisotropy was also higher than in gallbladders with pigment stones, reflecting lower membrane fluidity in ga llbladders with cholesterol stones. After muscle cells from cholesterol sto ne gallbladders were incubated with cholesterol-free liposomes for 4 hours, cholecystokinin octapeptide-induced contraction, membrane cholesterol cont ent and cholesterol/phospholipid ratio, and membrane fluidity returned to n ormal levels. Conclusions: Gallbladder muscle from patients with cholestero l stones has increased membrane cholesterol/phospholipid mole ratio and dec reased membrane fluidity resulting in impaired muscle contractility. These abnormalities are corrected by removing the excess cholesterol from the pla sma membranes.