Protons inhibit the BKCa channel of rat small artery smooth muscle cells

The regulation of the activity of calcium-activated potassium (BKCa) channe ls by intracellular proton ions (pH(i)) was investigated using the patch-cl amp technique in smooth muscle cells freshly isolated from rat tail small a rteries. Single-channel conductance and voltage dependence of activation we re not different at pH(i) 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) (mea n +/- SE) at pH(i) 7.4 and 54 +/- 2 mV (n = 4) at pHi 7.8 under conditions of pCa 5.9, and 30 +/- 5 mV (n = 5) at pH(i) 7.4 and 62 +/- 4 mV (n = 5) at pH(i) 7.0 under conditions of pCa 5.4. Furthermore, at a membrane potentia l of 0 mV, the pD(2) for intracellular calcium ions was 5.19 +/- 0.04 (n = 26) (mean +/- SD) at pH(i) 7.8, 5.02 +/- 0.05 (n = 28) at pH(i) 7.4, and 4. 82 +/- 0.05 (0 = 30) at pH(i) 7.0. In addition, an alteration of pH(i) resu lted in a profound change in the amplitude of BKCa 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 extrac ellular NH4Cl concentration to decrease the calculated pH(i) from 7.2 to 6. 8. Thus, alterations of pH(i) in the range from 7.0 to 7.8 did not affect s ingle-channel conductance and voltage dependence of activation but markedly altered single BKCa channel activity as well as intact cell BKCa current a mplitude, where an increase of the intracellular proton concentration inhib ited this channel. Copyright (C) 2001 S. Karger AG,Basel.