The regulation of the activity of calcium-activated potassium (BKCa) channels by intracellular proton ions (pHi) 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 pHi 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 pHi 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 pHi 7.4 and 62 ± 4 mV (n = 5) at pHi 7.0 under conditions of pCa 5.4. Furthermore, at a membrane potential of 0 mV, the pD2 for intracellular calcium ions was 5.19 ± 0.04 (n = 26) (mean ± SD) at pHi 7.8, 5.02 ± 0.05 (n = 28) at pHi 7.4, and 4.82 ± 0.05 (n = 30) at pHi 7.0. In addition, an alteration of pHi resulted 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 extracellular NH4Cl concentration to decrease the calculated pHi from 7.2 to 6.8. Thus, alterations of pHi in the range from 7.0 to 7.8 did not affect single-channel conductance and voltage dependence of activation but markedly altered single BKCa channel activity as well as intact cell BKCa current amplitude, where an increase of the intracellular proton concentration inhibited this channel.

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