Cell proliferation is associated with enhanced capacitative Ca2+ entry in human arterial myocytes

Vera A. Golovina


Depletion of Ca2+ stores in the sarcoplasmic reticulum (SR) activates extracellular Ca2+ influx via capacitative Ca2+ entry (CCE). Here, CCE levels in proliferating and growth-arrested human pulmonary artery smooth muscle cells (PASMCs) were compared by digital imaging fluorescence microscopy. Resting cytosolic free Ca2+ concentration ([Ca2+]cyt) in proliferating PASMCs was twofold higher than that in growth-arrested cells. Cyclopiazonic acid (CPA; 10 μM), which inhibits SR Ca2+-ATPase and depletes inositol 1,4,5-trisphosphate-sensitive Ca2+ stores, transiently increased [Ca2+]cytin the absence of extracellular Ca2+. The addition of 1.8 mM Ca2+ to the extracellular solution in the presence of CPA induced large increases in [Ca2+]cyt, indicative of CCE. The CPA-induced SR Ca2+ release in proliferating PASMCs was twofold higher than that in growth-arrested cells, whereas the transient rise of [Ca2+]cytdue to CCE was fivefold greater in proliferating cells. CCE was insensitive to nifedipine but was significantly inhibited by 50 mM K+, which reduces the driving force for Ca2+ influx, and by 0.5 mM Ni2+, a putative blocker of store-operated Ca2+ channels. These data show that augmented CCE is associated with proliferation of human PASMCs and may be involved in stimulating and maintaining cell growth.

  • vascular smooth muscle cells
  • growth factors
  • sarcoplasmic reticulum
  • digital imaging
  • fura 2


  • Address for reprint requests and other correspondence: V. A. Golovina, Dept. of Physiology, Univ. of Maryland School of Medicine, 655 West Baltimore St., Baltimore, MD 21201 (E-mail:vgolovin{at}umaryland.edu).

  • This work was supported by a grant from the American Heart Association, Mid-Atlantic Affiliate (to V. A. Golovina), and National Heart, Lung, and Blood Institute Grants HL-32276 (to M. P. Blaustein) and HL-54043 (to J. X.-J. Yuan).

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.

View Full Text