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Article
Signal Transduction Mechanisms of K+-Cl− Cotransport Regulation and Relationship to Disease
Acta Physiol
  • Norma C. Adragna, Wright State University - Main Campus
  • C. M. Ferrell, Wright State University - Main Campus
  • Jin Zhang, Wright State University - Main Campus
  • Mauricio Di Fulvio, Wright State University - Main Campus
  • C. F. Temprana
  • A. Sharma
  • Robert E.W. Fyffe, Wright State University
  • David R. Cool, Wright State University - Main Campus
  • Peter K. Lauf, Wright State University - Main Campus
Document Type
Article
Publication Date
5-1-2006
Abstract

The K+-Cl− cotransport (COT) regulatory pathways recently uncovered in our laboratory and their implication in disease state are reviewed. Three mechanisms of K+-Cl− COT regulation can be identified in vascular cells: (1) the Li+-sensitive pathway, (2) the platelet-derived growth factor (PDGF)-sensitive pathway and (3) the nitric oxide (NO)-dependent pathway. Ion fluxes, Western blotting, semi-quantitative RT-PCR, immunofluorescence and confocal microscopy were used. Li+, used in the treatment of manic depression, stimulates volume-sensitive K+-Cl− COT of low K+ sheep red blood cells at cellular concentrations <1 mM and inhibits at >3 mM, causes cell swelling, and appears to regulate K+-Cl− COT through a protein kinase C-dependent pathway. PDGF, a potent serum mitogen for vascular smooth muscle cells (VSMCs), regulates membrane transport and is involved in atherosclerosis. PDGF stimulates VSM K+-Cl− COT in a time- and concentration-dependent manner, both acutely and chronically, through the PDGF receptor. The acute effect occurs at the post-translational level whereas the chronic effect may involve regulation through gene expression. Regulation by PDGF involves the signalling molecules phosphoinositides 3-kinase and protein phosphatase-1. Finally, the NO/cGMP/protein kinase G pathway, involved in vasodilation and hence cardiovascular disease, regulates K+-Cl− COT in VSMCs at the mRNA expression and transport levels. A complex and diverse array of mechanisms and effectors regulate K+-Cl− COT and thus cell volume homeostasis, setting the stage for abnormalities at the genetic and/or regulatory level thus effecting or being affected by various pathological conditions.

DOI
10.1111/j.1748-1716.2006.01560.x
Citation Information
Norma C. Adragna, C. M. Ferrell, Jin Zhang, Mauricio Di Fulvio, et al.. "Signal Transduction Mechanisms of K+-Cl− Cotransport Regulation and Relationship to Disease" Acta Physiol Vol. 187 Iss. 1-2 (2006) p. 125 - 139 ISSN: 1748-1708
Available at: http://works.bepress.com/robert_fyffe/59/