|
|
|
|
|
|
|
||
Address correspondence to Clive M. Baumgarten, Department of Physiology, Medical College of Virginia, Box 980551 Richmond, VA 23298-0551. Fax: (804) 828-7382; email: clive.baumgarten{at}vcu.edu
Osmotic swelling of cardiac myocytes and other types of cells activates an outwardly rectifying, tamoxifen-sensitive Cl- current, ICl,swell, but it is unclear whether Cl- currents also are activated by direct mechanical stretch. We tested whether specific stretch of ß1-integrin activates a Cl- current in rabbit left ventricular myocytes. Paramagnetic beads (4.5-µm diameter) coated with mAb to ß1-integrin were applied to the surface of myocytes and pulled upward with an electromagnet while recording whole-cell current. In solutions designed to isolate anion currents, ß1-integrin stretch elicited an outwardly rectifying Cl- current with biophysical and pharmacological properties similar to those of ICl,swell. Stretch-activated Cl- current activated slowly (t1/2 = 3.5 ± 0.1 min), partially inactivated at positive voltages, reversed near ECl, and was blocked by 10 µM tamoxifen. When stretch was terminated, 64 ± 8% of the stretch-induced current reversed within 10 min. Mechanotransduction involved protein tyrosine kinase. Genistein (100 µM), a protein tyrosine kinase inhibitor previously shown to suppress ICl,swell in myocytes, inhibited stretch-activated Cl- current by 62 ± 6% during continued stretch. Because focal adhesion kinase and Src are known to be activated by cell swelling, mechanical stretch, and clustering of integrins, we tested whether these tyrosine kinases mediated the response to ß1-integrin stretch. PP2 (10 µM), a selective blocker of focal adhesion kinase and Src, fully inhibited the stretch-activated Cl- current as well as part of the background Cl- current, whereas its inactive analogue PP3 (10 µM) had no significant effect. In addition to activating Cl- current, stretch of ß1-integrin also appeared to activate a nonselective cation current and to suppress IK1. Integrins are the primary mechanical link between the extracellular matrix and cytoskeleton. The present results suggest that integrin stretch may contribute to mechano-electric feedback in heart, modulate electrical activity, and influence the propensity for arrhythmogenesis.
Key Words: stretch-activated channels • swelling-activated channels • mechano-electric feedback • protein tyrosine kinase • arrhythmia
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. K. Hoffmann, I. H. Lambert, and S. F. Pedersen Physiology of Cell Volume Regulation in Vertebrates Physiol Rev, January 1, 2009; 89(1): 193 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Hartzell, Z. Qu, K. Yu, Q. Xiao, and L.-T. Chien Molecular Physiology of Bestrophins: Multifunctional Membrane Proteins Linked to Best Disease and Other Retinopathies Physiol Rev, April 1, 2008; 88(2): 639 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Alessandri-Haber, O. A. Dina, E. K. Joseph, D. B. Reichling, and J. D. Levine Interaction of Transient Receptor Potential Vanilloid 4, Integrin, and Src Tyrosine Kinase in Mechanical Hyperalgesia J. Neurosci., January 30, 2008; 28(5): 1046 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Li, Q. Zhang, B. Teng, S. J. Mustafa, J.-Y. Huang, and H.-G. Yu Src tyrosine kinase alters gating of hyperpolarization-activated HCN4 pacemaker channel through Tyr531 Am J Physiol Cell Physiol, January 1, 2008; 294(1): C355 - C362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Kim and Y. E. Earm Journeying down the long and winding road: the whole picture of volume-activated Cl- channel activation in cardiac myocytes Cardiovasc Res, January 1, 2008; 77(1): 6 - 7. [Full Text] [PDF]
|
|
|
|
|
|
Z. Ren, F. J. Raucci Jr., D. M. Browe, and C. M. Baumgarten Regulation of swelling-activated Cl- current by angiotensin II signalling and NADPH oxidase in rabbit ventricle Cardiovasc Res, January 1, 2008; 77(1): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nishimura, Y. Kawai, T. Nakajima, Y. Hosoya, H. Fujita, M. Katoh, H. Yamashita, R. Nagai, and S. Sugiura Membrane potential of rat ventricular myocytes responds to axial stretch in phase, amplitude and speed-dependent manners Cardiovasc Res, December 1, 2006; 72(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lamitina, C. G. Huang, and K. Strange Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression PNAS, August 8, 2006; 103(32): 12173 - 12178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Pedersen, M. E. O'Donnell, S. E. Anderson, and P. M. Cala Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R1 - R25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Browe and C. M. Baumgarten EGFR Kinase Regulates Volume-sensitive Chloride Current Elicited by Integrin Stretch via PI-3K and NADPH Oxidase in Ventricular Myocytes J. Gen. Physiol., February 27, 2006; 127(3): 237 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Walsh and J. Zhang Regulation of cardiac volume-sensitive chloride channel by focal adhesion kinase and Src kinase Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2566 - H2574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ren and C. M. Baumgarten Antagonistic regulation of swelling-activated Cl- current in rabbit ventricle by Src and EGFR protein tyrosine kinases Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2628 - H2636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Cohen SRC family kinases in cell volume regulation Am J Physiol Cell Physiol, March 1, 2005; 288(3): C483 - C493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Healy and A. D. McCulloch An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes Europace, January 1, 2005; 7(s2): S128 - S134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Browe and C. M. Baumgarten Angiotensin II (AT1) Receptors and NADPH Oxidase Regulate Cl- Current Elicited by {beta}1 Integrin Stretch in Rabbit Ventricular Myocytes J. Gen. Physiol., August 30, 2004; 124(3): 273 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Larkin, D. Murphy, D. F. Reilly, M. Cahill, E. Sattler, P. Harriott, D. J. Cahill, and N. Moran ICln, a Novel Integrin {alpha}IIb{beta}3-Associated Protein, Functionally Regulates Platelet Activation J. Biol. Chem., June 25, 2004; 279(26): 27286 - 27293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Du, Z. Gao, C.-P. Lau, S.-W. Chiu, H.-F. Tse, C. M. Baumgarten, and G.-R. Li Differential Effects of Tyrosine Kinase Inhibitors on Volume-sensitive Chloride Current in Human Atrial Myocytes: Evidence for Dual Regulation by Src and EGFR Kinases J. Gen. Physiol., March 29, 2004; 123(4): 427 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
