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      Separation of two Cl Currents in Cultured Human and Murine Mesangial Cells: Biophysical and Pharmacological Characteristics of I Cl.vol and I Cl.Ca

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          Mesangial cells, a combined smooth muscle- and fibroblast-like phenotype, are important regulators of renal function. These cells exist in a region of variable osmolarity and may require Cl<sup>–</sup> channels for volume regulation. Additionally, Ca<sup>2+</sup>-activated Cl<sup>–</sup> channels in these cells may participate in Ca<sup>2+</sup>-dependent contractile responses to vasoactive agonists. Relatively little, however, is known about mesangial cell Cl<sup>–</sup> currents (I<sub>Cl</sub>); including the biophysical description and pharmacological characterization. We used whole-cell patch clamp to study I<sub>Cl</sub> in cultured human and SV40-transformed murine mesangial cells. I<sub>Cl</sub> was measured in cells dialyzed and bathed with symmetrical N-methyl- D-glucamine chloride solutions to minimize cation currents. Dialysis with buffers to control intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>), extracellular solutions of varied osmolarity, and manipulation of the transmembrane Cl<sup>–</sup> gradient were used to separate two currents: I<sub>Cl.vol</sub> (volume-sensitive), and I<sub>Cl.Ca</sub> (Ca<sup>2+</sup>-activated). In symmetrical Cl<sup>–</sup> with low [Ca<sup>2+</sup>]<sub>i</sub>, I<sub>Cl.vol</sub> was outwardly rectifying and modulated by osmolarity. I<sub>Cl.vol</sub> demonstrated slight time- and voltage-dependent inactivation. In symmetrical Cl<sup>–</sup> with elevated [Ca<sup>2+</sup>]<sub>i</sub> and hypertonic bath, I<sub>Cl.Ca</sub> was linear, but in asymmetrical Cl<sup>–</sup> (low [Cl<sup>–</sup>]<sub>i</sub>) was outwardly rectifying and demonstrated time- and voltage-dependent activation. Permeability sequences for both I<sub>Cl.vol</sub> and I<sub>Cl.Ca</sub> were I<sup>–</sup> > Br<sup>–</sup> > Cl<sup>–</sup> > F<sup>–</sup>; however, there were differences in the relative magnitudes. Tamoxifen inhibited I<sub>Cl.vol</sub> more potently than I<sub>Cl.Ca</sub>, whereas niflumic acid inhibited I<sub>Cl.Ca</sub> more potently than I<sub>Cl.vol</sub>. We have separated and characterized two types of I<sub>Cl</sub> in cultured human and murine mesangial cells. I<sub>Cl.Ca</sub> and I<sub>Cl.vol</sub> have different biophysical and pharmacological characteristics. These observations on I<sub>Cl.Ca</sub> and I<sub>Cl.vol</sub> may provide insight into mesangial cell reactivity and volume regulation.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          October 2002
          18 September 2002
          : 39
          : 5
          : 426-436
          Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nev., USA
          64516 J Vasc Res 2002;39:426–436
          © 2002 S. Karger AG, Basel

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          Page count
          Figures: 6, References: 40, Pages: 11
          Research Paper


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