help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on January 31, 2008, doi:10.1165/rcmb.2007-0395OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 6, June 2008, 744-749

A more recent version of this article appeared on June 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0395OCv1
38/6/744    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Peel, S. E
Right arrow Articles by Hall, I. P
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peel, S. E
Right arrow Articles by Hall, I. P

Submitted on November 2, 2007
Revised on January 29, 2008

ORAI and Store Operated Calcium Influx in Human Airway Smooth Muscle Cells

Samantha E Peel1, Bo Liu1, and Ian P Hall1*

1 Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, Nottingham, United Kingdom

* To whom correspondence should be addressed. E-mail: Ian.Hall{at}nottingham.ac.uk.

The initial bronchoconstrictor response of the asthmatic airway depends upon airway smooth muscle(ASM) contraction. Intracellular calcium is a key signalling molecule, mediating a number of responses including proliferation, gene expression and contraction of ASM. Ca2+ influx through receptor operated calcium(ROC) or store operated calcium(SOC) channels is thought to mediate longer term signals. The mechanisms of SOC activation in ASM remain to be elucidated. Recent literature has identified the STIM and ORAI proteins as key signalling players in the activation of the SOC subtype; calcium release activated channel current (ICRAC) in a number of inflammatory cell types. However the role for these proteins in activation of SOC in smooth muscle is unclear. We have previously demonstrated a role for STIM1 in SOC channel activation in human ASM (HASM). The aim of this study was to investigate the expression and define the potential roles of the ORAI proteins in SOC associated Ca2+ influx in HASM cells. Here we show that knockdown of ORAI1 by siRNA resulted in reduced thapsigargin (TG) or cyclopiazonic acid (CPA) induced Ca2+ influx, without affecting Ca2+ release from stores or basal levels. CPA induced inward currents were also reduced in the ORAI1 knockdown cells. We propose that ORAI1, along with STIM1 are important contributors to SOC entry in ASM cells. These data extend the major tissue types in which these proteins appear to be major determinants of SOC influx, and suggest that modulation of these pathways may prove useful in the treatment of bronchoconstriction.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Schindl, I. Frischauf, J. Bergsmann, M. Muik, I. Derler, B. Lackner, K. Groschner, and C. Romanin
Plasticity in Ca2+ selectivity of Orai1/Orai3 heteromeric channel
PNAS, November 17, 2009; 106(46): 19623 - 19628.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. G. Baryshnikov, M. V. Pulina, A. Zulian, C. I. Linde, and V. A. Golovina
Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger and plasma membrane Ca2+ pump in proliferating human arterial myocytes
Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1103 - C1112.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. Potier, J. C. Gonzalez, R. K. Motiani, I. F. Abdullaev, J. M. Bisaillon, H. A. Singer, and M. Trebak
Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration
FASEB J, August 1, 2009; 23(8): 2425 - 2437.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Lu, J. Wang, G. Peng, L. A. Shimoda, and J. T. Sylvester
Knockdown of stromal interaction molecule 1 attenuates store-operated Ca2+ entry and Ca2+ responses to acute hypoxia in pulmonary arterial smooth muscle
Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L17 - L25.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Agrotis and C. Koulis
STIM1: a new therapeutic target in occlusive vascular disease?
Cardiovasc Res, March 1, 2009; 81(4): 627 - 628.
[Full Text] [PDF]

Home page
 HypertensionHome page
F. R.C. Giachini, C.-W. Chiao, F. S. Carneiro, V. V. Lima, Z. N. Carneiro, A. M. Dorrance, R. C. Tostes, and R. C. Webb
Increased Activation of Stromal Interaction Molecule-1/Orai-1 in Aorta From Hypertensive Rats: A Novel Insight Into Vascular Dysfunction
Hypertension, February 1, 2009; 53(2): 409 - 416.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
A. D. Lyfenko and R. T. Dirksen
Differential dependence of store-operated and excitation-coupled Ca2+ entry in skeletal muscle on STIM1 and Orai1
J. Physiol., October 15, 2008; 586(20): 4815 - 4824.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
R. Berra-Romani, A. Mazzocco-Spezzia, M. V. Pulina, and V. A. Golovina
Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture
Am J Physiol Cell Physiol, September 1, 2008; 295(3): C779 - C790.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2008 American Thoracic Society. 		  Membership Renewal