Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity.
OBJECTIVE
The relationship between muscle contractility, plasma membrane cholesterol, and fluidity was investigated in human gallbladders with gallstones.


METHODS
Isolated gallbladder muscle cells were used to measure contraction. Plasma membranes of gallbladder muscle were purified in a sucrose gradient and measured for cholesterol content and cholesterol/phospholipid mole ratio. Membrane fluidity was determined by using fluorescence polarization and was expressed as the reciprocal of anisotropy.


RESULTS
The maximal contraction induced by cholecystokinin octapeptide was significantly 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 than in those with pigment stones. Membrane anisotropy was also higher than in gallbladders with pigment stones, reflecting lower membrane fluidity in gallbladders with cholesterol stones. After muscle cells from cholesterol stone gallbladders were incubated with cholesterol-free liposomes for 4 hours, cholecystokinin octapeptide-induced contraction, membrane cholesterol content and cholesterol/phospholipid ratio, and membrane fluidity returned to normal levels.


CONCLUSIONS
Gallbladder muscle from patients with cholesterol stones has increased membrane cholesterol/phospholipid mole ratio and decreased membrane fluidity resulting in impaired muscle contractility. These abnormalities are corrected by removing the excess cholesterol from the plasma membranes.
Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island, USA.
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Q
Chen
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J
Amaral
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Biancani
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J
Behar
D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D017081:Cholecystectomy, Laparoscopic; D002769:Cholelithiasis / Q000503:physiopathology*; D002784:Cholesterol / Q000032:analysis / Q000502:physiology*; D005454:Fluorescence Polarization; D005704:Gallbladder / Q000503:physiopathology*; D006801:Humans; D008081:Liposomes; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D010743:Phospholipids / Q000032:analysis
D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D002784:Cholesterol