| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Asthma Research Group, Firestone Institute for Respiratory Health, Saint Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5; and 2Toronto Lung Transplant Program, Division of Thoracic Surgery, University of Toronto, Ontario M5G 2C4, Canada
Submitted 6 April 2004 ; accepted in final form 16 June 2004
Airway smooth muscle (ASM) cells express voltage-dependent Ca2+ channels, primarily of the L-subtype. These may play a role in excitation-contraction coupling of ASM, although other signaling pathways may also contribute: one of these includes Rho and its downstream effector molecule Rho-associated kinase (ROCK). Although voltage-dependent Ca2+ influx and Rho/ROCK signaling have traditionally been viewed as entirely separate pathways, recent evidence in vascular smooth muscle suggest differently. In this study, we monitored contractile activity (muscle baths) in bronchial and/or tracheal preparations from the pig, cow, and human, and further examined Rho and ROCK activities (Western blots and kinase assays) and cytosolic levels of Ca2+ (fluo 4-based fluorimetry) in porcine tracheal myocytes. KCl evoked substantial contractions that were suppressed in tracheal preparations by removal of external Ca2+ or using the selective L-type Ca2+ channel blocker nifedipine; porcine bronchial preparations were much less sensitive, and bovine bronchi were essentially unaffected by 1 µM nifedipine. Surprisingly, KCl-evoked contractions were also highly sensitive to two structurally different ROCK inhibitors: Y-27632 and HA-1077. Furthermore, the inhibitory effects of nifedipine and of the ROCK inhibitors were not additive. KCl also caused marked stimulation of Rho and ROCK activities, and both these changes were suppressed by nifedipine or by removal of external Ca2+. KCl-induced elevation of [Ca2+]i was not affected by Y-27632 but was reversed by NiCl2 or by BAPTA-AM. We conclude that KCl acts in part through stimulation of Rho and ROCK, possibly secondary to voltage-dependent Ca2+ influx.
myosin light chain phosphatase; Rho; Rho-associated kinase; voltage-dependent calcium channels
This article has been cited by other articles:
|
|
 |
|
  C. Morin, C. Guibert, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Effects of {omega}-hydroxylase product on distal human pulmonary arteries Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1435 - H1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, L. Weigand, J. Foxson, L. A. Shimoda, and J. T. Sylvester Ca2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L674 - L685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hirota, P. Helli, and L. J. Janssen Ionic mechanisms and Ca2+ handling in airway smooth muscle Eur. Respir. J., July 1, 2007; 30(1): 114 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Wardle, M. Gu, Y. Ishida, and R. J. Paul Rho kinase is an effector underlying Ca2+-desensitizing hypoxic relaxation in porcine coronary artery Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H23 - H29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Epoxyeicosatrienoic Acid Relaxing Effects Involve Ca2+-Activated K+ Channel Activation and CPI-17 Dephosphorylation in Human Bronchi Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 633 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gao, A. D. Portugal, S. Negash, W. Zhou, L. D. Longo, and J. Usha Raj Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L678 - L684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hirota, E. Pertens, and L. J. Janssen The reverse mode of the Na+/Ca2+ exchanger provides a source of Ca2+ for store refilling following agonist-induced Ca2+ mobilization Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L438 - L447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bai, M. Zhang, and M. J. Sanderson Contractility and Ca2+ Signaling of Smooth Muscle Cells in Different Generations of Mouse Airways Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 122 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, T. Tazzeo, and L. J. Janssen Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+ handling and Rho/ROCK signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1177 - L1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, J. Zuo, and L. J. Janssen Regulation of airway smooth muscle RhoA/ROCK activities by cholinergic and bronchodilator stimuli Eur. Respir. J., October 1, 2006; 28(4): 703 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Wardle, M. Gu, Y. Ishida, and R. J. Paul Ca2+-desensitizing hypoxic vasorelaxation: pivotal role for the myosin binding subunit of myosin phosphatase (MYPT1) in porcine coronary artery J. Physiol., April 1, 2006; 572(1): 259 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Melton, A. Datta, and H. F. Yee Jr. [Ca2+]i-independent contractile force generation by rat hepatic stellate cells in response to endothelin-1 Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G7 - G13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, J. Zuo, E. Pertens, P. B. Helli, and L. J. Janssen Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca2+]i Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L574 - L582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Ratz, K. M. Berg, N. H. Urban, and A. S. Miner Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus Am J Physiol Cell Physiol, April 1, 2005; 288(4): C769 - C783. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
