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ATP-sensitive K+ channel opener acts as a potent Cl− channel inhibitor in vascular smooth muscle cells
- Source :
- Journal of Membrane Biology; January 1994, Vol. 137 Issue: 1 p59-70, 12p
- Publication Year :
- 1994
-
Abstract
- Abstract: We describe the activation of a K<superscript>+</superscript> current and inhibition of a Cl<superscript>–</superscript> current by a cyanoguanidine activator of ATP-sensitive K<superscript>+</superscript> channels (K<subscript>ATP</subscript>) in the smooth muscle cell line A10. The efficacy of U83757, an analogue of pinacidil, as an activator of K<subscript>ATP</subscript> was confirmed in single channel experiments on isolated ventricular myocytes. The effects of U83757 were examined in the clonal smooth muscle cell line A10 using voltage-sensitive dyes and digital fluorescent imaging techniques. Exposure of A10 cells to U83757 (10 nm to 1 mgrm) produced a rapid membrane hyperpolarization as monitored by the membrane potential-sensitive dye bis-oxonol ([diBAC<subscript>4</subscript>(3)], 5 mgrm). The U83757induced hyperpolarization was antagonized by glyburide and tetrapropylammonium (TPrA) but not by tetraethlylammonium (TEA) or charybdotoxin (ChTX). The molecular basis of the observed hyperpolarization was studied in whole-cell, voltage-clamp experiments. Exposure of voltage-clamped cells to U83757 (300 nm to 300 mgrm) produced a hyperpolarizing shift in the zero current potential; however, the hyperpolarizing shift in reversal potential was associated with either an increase or decrease in membrane conductance. In solutions where E <subscript>k</subscript>=–82 mV and E <subscript>Cl</subscript>=0 mV, the reversal potential of the U83757-sensitive current was approximately –70 mV in those experiments where an increase in membrane conductance was observed. In experiments in which a decrease in conductance was observed, the reversal potential of the U83757-sensitive current was approximately 0 mV, suggesting that U83757 might be acting as a Cl<superscript>–</superscript> channel blocker as well as a K<superscript>+</superscript> channel opener. In experiments in which Cl<superscript>–</superscript> current activation was specifically brought about by cellular swelling and performed in solutions where Cl<superscript>–</superscript> was the major permeant ion, U83757 (300 nm to 300 mgrm) produced a dose-dependent current inhibition. Taken together these results (i) demonstrate the presence of a K<superscript>+</superscript>-selective current which is sensitive to K<subscript>ATP</subscript> channel openers in A10 cells and (ii) indicate that the hyperpolarizing effects of K<superscript>+</superscript> channel openers in vascular smooth muscle may be due to both the inhibition of Cl<superscript>–</superscript> currents as well as the activation of a K<superscript>+</superscript>-selective current.
Details
- Language :
- English
- ISSN :
- 00222631 and 14321424
- Volume :
- 137
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Journal of Membrane Biology
- Publication Type :
- Periodical
- Accession number :
- ejs15518709
- Full Text :
- https://doi.org/10.1007/BF00234998