AJP - Cell Physiology, Vol 257, Issue 2 C306-C314, Copyright © 1989 by American Physiological Society

ARTICLES

Excess membrane cholesterol alters calcium channels in arterial smooth muscle

R. A. Bialecki and T. N. Tulenko
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.

We studied the effects of cholesterol enrichment on arterial function by evaluating its effects on 45Ca2+ uptake and tension development in the carotid artery of the rabbit. Arterial segments were enriched with cholesterol in vitro, using media containing liposomes composed of free (unesterified) cholesterol (FC) and phospholipid (PL) in a 2:1 molar ratio. Control segments were simultaneously perfused with 0.5:1 liposomal medium to compare the possible effects of PL. Rings from these arteries were then tested for basal and activated Ca2+ uptake and for contractile responses to norepinephrine (NE) and KCl. We found elevated 45Ca2+ uptake under basal and NE-activated conditions along with an increased contractile sensitivity (4-fold) to NE. These alterations correlated with a 78% increase in the FC/PL ratio reflecting cholesterol enrichment of cellular membranes. Cholesterol enrichment did not alter resting or maximal tensions, K+-activated Ca2+ uptake, or contractile sensitivity to K+. Pretreatment with 1 microM diltiazem abolished the cholesterol-induced increase in basal as well as NE-activated 45Ca2+ uptake but had no effect on either uptake in control vessels. These studies suggest that excess membrane cholesterol selectively increases NE contractile sensitivity by increasing basal or NE-activated Ca2+ influx (or both) as a result of fundamental alteration in the calcium channels in arterial smooth muscle cell membrane.

This article has been cited by other articles:

				Z. Xiao, F. Schmitz, V. E. Pricolo, P. Biancani, and J. Behar Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1641 - G1649. [Abstract] [Full Text] [PDF]

				C. M. C. Dupasquier, A.-M. Weber, B. P. Ander, P. P. Rampersad, S. Steigerwald, J. T. Wigle, R. W. Mitchell, E. A. Kroeger, J. S. C. Gilchrist, M. M. Moghadasian, et al. Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2987 - H2996. [Abstract] [Full Text] [PDF]

				C. Balut, P. Steels, M. Radu, M. Ameloot, W. V. Driessche, and D. Jans Membrane cholesterol extraction decreases Na+ transport in A6 renal epithelia Am J Physiol Cell Physiol, January 1, 2006; 290(1): C87 - C94. [Abstract] [Full Text] [PDF]

				Z.-L. Xiao, J. Amaral, P. Biancani, and J. Behar Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones Am J Physiol Gastrointest Liver Physiol, March 1, 2005; 288(3): G525 - G532. [Abstract] [Full Text] [PDF]

				D. W. Wilde, K. D. Massey, G. K. Walker, A. Vollmer, and R. J. Grekin High-Fat Diet Elevates Blood Pressure and Cerebrovascular Muscle Ca2+ Current Hypertension, March 1, 2000; 35(3): 832 - 837. [Abstract] [Full Text] [PDF]

				Z.-L. Xiao, Q. Chen, J. Amaral, P. Biancani, and J. Behar Defect of receptor-G protein coupling in human gallbladder with cholesterol stones Am J Physiol Gastrointest Liver Physiol, February 1, 2000; 278(2): G251 - G258. [Abstract] [Full Text] [PDF]

				M. S.F. Clarke, M. A. Prendergast, and A. V. Terry Jr. Plasma Membrane Ordering Agent Pluronic F-68 (PF-68) Reduces Neurotransmitter Uptake and Release and Produces Learning and Memory Deficits in Rats Learn. Mem., November 1, 1999; 6(6): 634 - 649. [Abstract] [Full Text]

				C. Wilson, S.-J. Hunt, E. Tang, N. Wright, E. Kelly, S. Palmer, C. Heys, S. Mellor, R. James, and R. Bialecki Pharmacological Profile of ZD1611, a Novel, Orally Active Endothelin ETA Receptor Antagonist J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1085 - 1091. [Abstract] [Full Text]

				Q-W Xu, R B Scott, D T M Tan, and E A Shaffer Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin Gut, December 1, 1998; 43(6): 817 - 822. [Abstract] [Full Text] [PDF]

				T. N. Tulenko, M. Chen, P. E. Mason, and R. P. Mason Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis J. Lipid Res., May 1, 1998; 39(5): 947 - 956. [Abstract] [Full Text]

				R. A. Bialecki, C. S. Fisher, W. W. Murdoch, H. G. Barthlow, R. B. Stow, M. Mallamaci, and W. Rumsey Hypoxic exposure time dependently modulates endothelininduced contraction of pulmonary artery smooth muscle Am J Physiol Lung Cell Mol Physiol, April 1, 1998; 274(4): L552 - L559. [Abstract] [Full Text] [PDF]

				G. Nickenig, A. Sachinidis, F. Michaelsen, M. Bohm, S. Seewald, and H. Vetter Upregulation of Vascular Angiotensin II Receptor Gene Expression by Low-Density Lipoprotein in Vascular Smooth Muscle Cells Circulation, January 21, 1997; 95(2): 473 - 478. [Abstract] [Full Text]

				C. L. Cowan and R. P. Steffen Lysophosphatidylcholine Inhibits Relaxation of Rabbit Abdominal Aorta Mediated by Endothelium-Derived Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor Independent of Protein Kinase C Activation Arterioscler. Thromb. Vasc. Biol., December 1, 1995; 15(12): 2290 - 2297. [Abstract] [Full Text]