Effect of hypercholesterolaemia on voltage-operated calcium channel currents in rabbit arterial smooth muscle cells.
Cholesterol is a major component of cell membranes and influences membrane fluidity. Watanabe heritable hyperpercholesterolaemic rabbits (WHHL) possess defective receptors for low density lipoprotein leading to increased plasma cholesterol, accumulation of cholesterol in the arterial wall and atherosclerosis. In this study calcium channel currents (IBa) were compared using conventional whole cell voltage clamp techniques in ear artery cells isolated from control New Zealand White rabbits (NZ) with those from WHHL. IBa were larger in cells isolated from NZ than from WHHL, however cell capacitance was also greater in NZ cells. Consequently, there was no significant difference in current density between NZ and WHHL cells either in the absence of drug or in the presence of the calcium channel agonist (+)202 791. Current voltage-relationships, kinetics of fast inactivation and steady-state inactivation of IBa also did not differ significantly between WHHL and NZ. These findings suggest that hypercholesterolaemia in WHHL has no direct effect on calcium channel current density or voltage-modulation in arterial smooth muscle cells.
Clunn
G F
GF
Clinical Pharmacology, NHLI, St. Mary's Hospital, Imperial College of Science, Technology and Medicine, South Wharf Road, London, W2 1NY, UK.
Wijetunge
S
S
Hughes
A D
AD
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity
D015220:Calcium Channels; D008077:Lipoproteins, LDL