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      Protons Inhibit the BK Ca Channel of Rat Small Artery Smooth Muscle Cells


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          The regulation of the activity of calcium-activated potassium (BK<sub>Ca</sub>) channels by intracellular proton ions (pH<sub>i</sub>) was investigated using the patch-clamp technique in smooth muscle cells freshly isolated from rat tail small arteries. Single-channel conductance and voltage dependence of activation were not different at pH<sub>i</sub> 7.0, 7.4 and 7.8. However, the membrane potential at which channel open probability reached 0.5 was 74 ± 5 mV (n = 6) (mean ± SE) at pH<sub>i</sub> 7.4 and 54 ± 2 mV (n = 4) at pH<sub>i</sub> 7.8 under conditions of pCa 5.9, and 30 ± 5 mV (n = 5) at pH<sub>i</sub> 7.4 and 62 ± 4 mV (n = 5) at pH<sub>i</sub> 7.0 under conditions of pCa 5.4. Furthermore, at a membrane potential of 0 mV, the pD<sub>2</sub> for intracellular calcium ions was 5.19 ± 0.04 (n = 26) (mean ± SD) at pH<sub>i</sub> 7.8, 5.02 ± 0.05 (n = 28) at pH<sub>i</sub> 7.4, and 4.82 ± 0.05 (n = 30) at pH<sub>i</sub> 7.0. In addition, an alteration of pH<sub>i</sub> resulted in a profound change in the amplitude of BK<sub>Ca</sub> currents in intact cells; it reversibly attenuated the current-voltage relationship decreasing the current by 55 ± 3% (n = 7) (p < 0.001) at 70 mV after lowering the extracellular NH<sub>4</sub>Cl concentration to decrease the calculated pH<sub>i</sub> from 7.2 to 6.8. Thus, alterations of pH<sub>i</sub> in the range from 7.0 to 7.8 did not affect single-channel conductance and voltage dependence of activation but markedly altered single BK<sub>Ca</sub> channel activity as well as intact cell BK<sub>Ca</sub> current amplitude, where an increase of the intracellular proton concentration inhibited this channel.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          February 2001
          08 February 2001
          : 38
          : 1
          : 30-38
          aInstitute of Physiology, University of Rostock, Germany, and bInstitute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria
          51027 J Vasc Res 2001;38:30–38
          © 2001 S. Karger AG, Basel

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          Page count
          Figures: 5, References: 21, Pages: 9
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Vascular smooth muscle,Intracellular pH,Calcium-activated potassium channel,Patch-clamp


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