Published online before print January 31, 2002, doi: 10.1161/hh0402.105899
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 10, 2001
Revised on January 17, 2002
Accepted on January 17, 2002
4ß1 Integrin Activation of L-Type Calcium Channels in Vascular Smooth Muscle Causes Arteriole Vasoconstriction
Kelli R. Waitkus-Edwards ;
From the Department of Medical Physiology (K.R.W.-E., L.A.M.-L., X.W., M.J.D., G.A.M.), the Department of Medical Pharmacology and Toxicology (J.P.T.), and the Department of Pathology and Laboratory Medicine (G.E.D.), Cardiovascular Research Institute, Division of Vascular Biology, Texas A&M University System Health Science Center, College Station, Tex.
* To whom correspondence should be addressed. E-mail: gam{at}tamu.edu.
A pathway for the regulation of vascular tone appears to involve coupling between integrins and extracellular matrix proteins or their fragments and the subsequent modulation of ion movement across the smooth muscle cell membrane. Here, we report that the activation of L-type voltage-activated Ca2+ channels occurs through a novel interaction of 4ß1 integrin with peptides containing the Leu-Asp-Val (LDV) integrin--binding sequence, which is found in the CS-1 region of an alternately spliced fibronectin variant. Experiments were conducted on arterioles isolated from rat skeletal muscle. Arterioles exhibited sustained concentration-dependent vasoconstriction to LDV peptides but not to Leu-Glu-Val (LEV) control peptides. The constriction was associated with increased smooth muscle cell [Ca2+]i, as measured by using fura 2. The response could be inhibited with a function-blocking anti--4 integrin antibody. Removal of the endothelium did not alter the vasoconstrictor response. Further experiments demonstrated that the vasoconstriction was abolished by the L-type Ca2+ channel inhibitor nifedipine and the Src family kinase inhibitor PP2. In studies of isolated smooth muscle cells using whole-cell patch-clamp methods, the L-type current was enhanced by the LDV but not LEV peptide and was blocked by PP2 or antibodies to 4 integrin. Collectively, these data indicate that activation of 4ß1 integrin leads to enhanced influx of Ca2+ through L-type channels by activating a tyrosine kinase pathway, leading to vasoconstriction. Involvement of integrins in the modulation of vascular tone may be particularly important in vascular responses to mechanical signals, such as pressure and flow, and to tissue injury after damage to the extracellular matrix.
Key words: voltage-gated Ca2+ channels • vascular smooth muscle • Leu-Asp-Val • fibronectin • extracellular matrix • Src family kinases • protein kinase C
This article has been cited by other articles:
 |
|
 |
|
  A. Mandal, M. Shahidullah, N. A. Delamere, and M. A. Teran Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes Am J Physiol Cell Physiol, July 1, 2009; 297(1): C111 - C120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shi, K. Jian, M. L. Ko, D. Trump, and G. Y.-P. Ko Retinoschisin, a New Binding Partner for L-type Voltage-gated Calcium Channels in the Retina J. Biol. Chem., February 6, 2009; 284(6): 3966 - 3975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Sun, L. A. Martinez-Lemus, M. A. Hill, and G. A. Meininger Extracellular matrix-specific focal adhesions in vascular smooth muscle produce mechanically active adhesion sites Am J Physiol Cell Physiol, July 1, 2008; 295(1): C268 - C278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Loufrani, K. Retailleau, A. Bocquet, O. Dumont, K. Danker, H. Louis, P. Lacolley, and D. Henrion Key role of {alpha}1{beta}1-integrin in the activation of PI3-kinase-Akt by flow (shear stress) in resistance arteries Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1906 - H1913. [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]
|
|
|
|
|
|
A. Umesh, M. A. Thompson, E. N. Chini, K.-P. Yip, and J. S. K. Sham Integrin Ligands Mobilize Ca2+ from Ryanodine Receptor-gated Stores and Lysosome-related Acidic Organelles in Pulmonary Arterial Smooth Muscle Cells J. Biol. Chem., November 10, 2006; 281(45): 34312 - 34323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akkawi, T. Nassar, M. Tarshis, D. B. Cines, and A. A.-R. Higazi LRP and {alpha}vbeta3 mediate tPA activation of smooth muscle cells Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1351 - H1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gui, X. Wu, S. Ling, S. C. Stotz, R. J. Winkfein, E. Wilson, G. E. Davis, A. P. Braun, G. W. Zamponi, and M. J. Davis Integrin Receptor Activation Triggers Converging Regulation of Cav1.2 Calcium Channels by c-Src and Protein Kinase A Pathways J. Biol. Chem., May 19, 2006; 281(20): 14015 - 14025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wenzel, A. Schmidt, K. Reimann, J. Hescheler, G. Pfitzer, W. Bloch, and B.K. Fleischmann Endostatin, the Proteolytic Fragment of Collagen XVIII, Induces Vasorelaxation Circ. Res., May 12, 2006; 98(9): 1203 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kanefsky, M. Lenburg, and C.-M. Hai Cholinergic Receptor and Cyclic Stretch-Mediated Inflammatory Gene Expression in Intact ASM Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 417 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Qamirani, H. M. Razavi, X. Wu, M. J. Davis, L. Kuo, and T. W. Hein Sodium azide dilates coronary arterioles via activation of inward rectifier K+ channels and Na+-K+-ATPase Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1617 - H1623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Huang, D. Sun, C. Yan, J. R. Falck, and G. Kaley Contribution of 20-HETE to Augmented Myogenic Constriction in Coronary Arteries of Endothelial NO Synthase Knockout Mice Hypertension, September 1, 2005; 46(3): 607 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lu, X.-L. Wang, T. He, W. Zhou, T. L. Kaduce, Z. S. Katusic, A. A. Spector, and H.-C. Lee Impaired Arachidonic Acid-Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats Diabetes, July 1, 2005; 54(7): 2155 - 2163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Martinez-Lemus, T. Crow, M. J. Davis, and G. A. Meininger {alpha}v{beta}3- and {alpha}5{beta}1-integrin blockade inhibits myogenic constriction of skeletal muscle resistance arterioles Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H322 - H329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Goncalves, W. S. Nesbitt, Y. Yuan, and S. P. Jackson Importance of Temporal Flow Gradients and Integrin {alpha}IIb{beta}3 Mechanotransduction for Shear Activation of Platelets J. Biol. Chem., April 15, 2005; 280(15): 15430 - 15437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Sarin, R. D Gaffin, G. A Meininger, and M. Muthuchamy Arginine-glycine-aspartic acid (RGD)-containing peptides inhibit the force production of mouse papillary muscle bundles via {alpha}5{beta}1 integrin J. Physiol., April 15, 2005; 564(2): 603 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V Vasilyev and M. E Barish Regulation of the hyperpolarization-activated cationic current Ih in mouse hippocampal pyramidal neurones by vitronectin, a component of extracellular matrix J. Physiol., November 1, 2004; 560(3): 659 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Rueckschloss and G. Isenberg Contraction augments L-type Ca2+ currents in adherent guinea-pig cardiomyocytes J. Physiol., October 15, 2004; 560(2): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Imadojemu, K. Mooney, C. Hogeman, M. E.J. Lott, A. Kunselman, and L. I. Sinoway Extracellular Calcium and Vascular Responses After Forearm Ischemia Circulation, July 6, 2004; 110(1): 79 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shiratsuchi and M. D. Basson Extracellular pressure stimulates macrophage phagocytosis by inhibiting a pathway involving FAK and ERK Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1358 - C1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K.W. Chew, J. M. Orshal, and R. A. Khalil Elastase-Induced Suppression of Endothelin-Mediated Ca2+ Entry Mechanisms of Vascular Contraction Hypertension, October 1, 2003; 42(4): 818 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V Vasilyev and M. E Barish Regulation of an inactivating potassium current (IA) by the extracellular matrix protein vitronectin in embryonic mouse hippocampal neurones J. Physiol., March 15, 2003; 547(3): 859 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Hool Can Integrins Integrate Vascular Myogenic Responses? Circ. Res., March 8, 2002; 90(4): 371 - 373. [Full Text] [PDF]
|
|