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Coordinated Regulation of Vascular Ca2+ and K+ Channels by Integrin Signaling

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Integrins and Ion Channels

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 674))

Abstract

A role for integrins in mechanotransduction has been suggested because these molecules form an important mechanical link between the extracellular matrix (ECM) and the cytoskeleton. An example of mechanotransduction in blood vessels is the myogenic response—the rapid and maintained constriction of arterioles in response to pressure elevation. L-type calcium channels and large-conductance, calcium-activated potassium (BK) channels are known to play important roles in the myogenic response and in the maintenance of myogenic (pressure-induced) vascular tone. Our recent studies on isolated, cannulated arterioles and freshly-dispersed arteriolar smooth muscle cells show that both L-type calcium channels (Cav1.2) and BK channels are regulated by α5β1 integrin activation. α5β1 integrin interacts with the ECM protein fibronectin, which is distributed in basement membrane and interstitial matrices surrounding smooth muscle cells within the arteriolar wall. Truncation and site-directed mutagenesis strategies reveal that regulation of Cav1.2 by α5β1 integrin requires phosphorylation of the channel α1C subunit at C-terminal residues Ser-1901 and Tyr-2122. Likewise, BK channel potentiation by α5β1 integrin activation requires c-Src phosphorylation of the channel α-subunit at residue Tyr-766. Thus, both L-type calcium channels and BK channels can be regulated coordinately through integrin-linked phosphorylation cascades involving c-Src. We propose that these two channels are under constitutive control by α5β1 integrin-fibronectin interactions in the vessel wall such that the balance of their activity determines myogenic tone and the vascular response to vessel wall injury/remodeling.

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Authors and Affiliations

  1. Dept. Medical Pharmacology and Physiology, University of Missouri School of Medicine, 1 Hospital Dr., Rm. M451, Columbia, Missouri, 65212, USA

    Peichun Gui, Jun-Tzu Chao, Yan Yang, George E. Davis & Michael J. Davis

  2. Department of Systems Biology and Translational Medicine, College of Medicine Texas A&M Health Science Center, College Station, Texas, USA

    Xin Wu

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  1. Peichun Gui
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  2. Jun-Tzu Chao
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  3. Xin Wu
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  4. Yan Yang
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  5. George E. Davis
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  6. Michael J. Davis
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Correspondence to Michael J. Davis .

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Editors and Affiliations

  1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy

    Andrea Becchetti PhD

  2. Department of Experimental Pathology and Oncology, University of Florence, Florence, Itlay

    Annarosa Arcangeli MD, PhD

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Gui, P., Chao, JT., Wu, X., Yang, Y., Davis, G.E., Davis, M.J. (2010). Coordinated Regulation of Vascular Ca2+ and K+ Channels by Integrin Signaling. In: Becchetti, A., Arcangeli, A. (eds) Integrins and Ion Channels. Advances in Experimental Medicine and Biology, vol 674. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6066-5_7

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