HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by YAO, X. Articles by HUANG, Y. Search for Related Content PubMed PubMed Citation Articles by YAO, X. Articles by HUANG, Y.

A protein kinase G-sensitive channel mediates flow-induced Ca²⁺ entry into vascular endothelial cells

X. YAO^*1, H. Y. KWAN^*, F. L. CHAN, N. W. K. CHAN^* and Y. HUANG^*

^* Department of Physiology,
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong

¹Correspondence: 319 BMSB, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: yao2068{at}cuhk.edu.hk

The hemodynamic force generated by blood flow is considered to be the physiologically most important stimulus for the release of nitric oxide (NO) and prostacyclin (PGI₂) from vascular endothelial cells (1). NO and PGI₂ then act on the underlying smooth muscle cells, causing vasodilation and thus lowering blood pressure (2, 3). One critical early event occurring in this flow-induced regulation of vascular tone is that blood flow induces Ca²⁺ entry into vascular endothelial cells, which in turn leads to the formation of NO (4, 5). Here we report a mechanosensitive Ca²⁺-permeable channel in vascular endothelial cells. The activity of the channel was inhibited by 8-Br-cGMP, a membrane-permeant activator of protein kinase G (PKG), in cell-attached membrane patches. The inhibition could be reversed by PKG inhibitor KT5823 or H-8. A direct application of active PKG in inside-out patches blocked the channel activity. Gd³⁺, Ni²⁺, or SK&F-96365 also inhibited the channel activity. A study of fluorescent Ca²⁺ entry revealed a striking pharmacological similarity between the Ca²⁺ entry elicited by flow and the mechanosensitive Ca²⁺-permeable channel we identified, suggesting that this channel is the primary pathway mediating flow-induced Ca²⁺ entry into vascular endothelial cells.—Yao, X., Kwan, H. Y., Chan, F. L., Chan, N. W. K., Huang, Y. A protein kinase G-sensitive channel mediates flow-induced Ca²⁺ entry into vascular endothelial cells.

Key Words: blood flow • shear stress • nonselective cation channel • endothelium

This article has been cited by other articles:

				X. Yao and C. J. Garland Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels Circ. Res., October 28, 2005; 97(9): 853 - 863. [Abstract] [Full Text] [PDF]

				Y. Hou, J. Lascola, N. O. Dulin, R. D. Ye, and D. D. Browning Activation of cGMP-dependent Protein Kinase by Protein Kinase C J. Biol. Chem., May 2, 2003; 278(19): 16706 - 16712. [Abstract] [Full Text] [PDF]

				H.-Y. Kwan, P.-C. Leung, Y. Huang, and X. Yao Depletion of Intracellular Ca2+ Stores Sensitizes the Flow-Induced Ca2+ Influx in Rat Endothelial Cells Circ. Res., February 21, 2003; 92(3): 286 - 292. [Abstract] [Full Text] [PDF]

				L. A. Shimoda, L. E. Welsh, and D. B. Pearse Inhibition of inwardly rectifying K+ channels by cGMP in pulmonary vascular endothelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L297 - L304. [Abstract] [Full Text] [PDF]

				E. E. Daniel, T. J. Bowes, and J. Jury Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 1111 - 1118. [Abstract] [Full Text] [PDF]

				J. L. Jiang, Q. Zhou, M. K. Yu, L. S. Ho, Z. N. Chen, and H. C. Chan The Involvement of HAb18G/CD147 in Regulation of Store-operated Calcium Entry and Metastasis of Human Hepatoma Cells J. Biol. Chem., December 7, 2001; 276(50): 46870 - 46877. [Abstract] [Full Text] [PDF]

				B. Nilius and G. Droogmans Ion Channels and Their Functional Role in Vascular Endothelium Physiol Rev, October 1, 2001; 81(4): 1415 - 1459. [Abstract] [Full Text] [PDF]

				H. Tanaka and T. Takamatsu Calcium Spots : Elementary Signals in Response to Mechanical Stress in Vascular Endothelial Cells Circ. Res., May 11, 2001; 88(9): 852 - 854. [Full Text] [PDF]

				K. A. Dora, C. J. Garland, H. Y. Kwan, and X. Yao Endothelial cell protein kinase G inhibits release of EDHF through a PKG-sensitive cation channel Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1272 - H1277. [Abstract] [Full Text] [PDF]

				Q.-K. Tran, K. Ohashi, and H. Watanabe Calcium signalling in endothelial cells Cardiovasc Res, October 1, 2000; 48(1): 13 - 22. [Abstract] [Full Text] [PDF]

				H. Y. Kwan, Y. Huang, S. K. Kong, and X. Yao cGMP abolishes agonist-induced [Ca2+]i oscillations in human bladder epithelial cells Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1067 - F1074. [Abstract] [Full Text] [PDF]

				H. Ohata, T. Ikeuchi, A. Kamada, M. Yamamoto, and K. Momose Lysophosphatidic Acid Positively Regulates the Fluid Flow-Induced Local Ca2+ Influx in Bovine Aortic Endothelial Cells Circ. Res., May 11, 2001; 88(9): 925 - 932. [Abstract] [Full Text] [PDF]