Published online before print May 6, 2004, doi: 10.1161/01.RES.0000131495.93500.3c
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© 2004 American Heart Association, Inc.
UltraRapid Communications |
High Blood Pressure Upregulates Arterial L-Type Ca2+ Channels
Is Membrane Depolarization the Signal?
From the Department of Pharmacology and Toxicology (A.P., M.P., N.J.R.), The Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wis; and the Department of Neurology (J.A.M.), Medical College of Wisconsin and Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wis.
Correspondence to Nancy J. Rusch, PhD, Prof, Department of Pharmacology and Toxicology Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail nrusch{at}mcw.edu
Long-lasting Ca2+ (CaL) channels of the Cav1.2 gene family contribute to the pathogenesis of abnormal arterial tone in hypertension. The physiological stimulus that enhances CaL channel current in the vascular smooth muscle cells (VSMCs) remains unknown. The present study investigated if high blood pressure triggers an upregulation of vascular CaL channel protein. Rat aortae were banded between the origins of the left renal (LR) and right renal (RR) arteries to selectively elevate blood pressure in the proximal RR arteries. After 2 days, the immunoreactivity on Western blots corresponding to the pore-forming 
1C subunit of the CaL channel was increased 3.25-fold in RR compared with LR arteries. This finding persisted at 28 days and was associated with abnormal Ca2+-dependent tone and higher CaL currents in the VSMCs exposed to high pressure. Based on microelectrode studies indicating that RR arteries were depolarized compared with LR arteries, further studies examined if membrane depolarization, an inherent response of VSMCs to high blood pressure, increased 1C expression. Isolated rat renal arteries were cultured for 2 days in low K+ (4 mmol/L) or depolarizing high K+ (30 mmol/L) media. Arteries preconditioned in high K+ showed a 5.47-fold increase in 1C expression, enhanced CaL channel current, and elevated Ca2+-dependent tone. These findings provide the first direct evidence that high blood pressure upregulates the CaL channel 1C subunit in VSMCs in vivo and suggest that membrane depolarization is a potential signal involved in this interaction that may contribute to the development of abnormal vascular tone.
Key Words: calcium channels • 1C subunit • membrane potential • vascular smooth muscle • hypertension
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