The effect of external pH on the delayed rectifying K+ current in cardiac ventricular myocytes
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The effects of extracellular pH (pHe) on the delayed rectifying K+ current i Kr in rabbit ventricular myocytes were studied using the whole-cell-clamp technique. Since a variety of results have been reported on the effect of pH on expressed hERG channels, our aim was to investigate the effects of pH on i Kr channels in their native environment. i Kr is reduced by extracellular acidification and its deactivation is faster. Extracellular acidification results in a marked shift of the steady-state activation curve to more positive potentials, while alkalinization does not produce a significant shift. E 1/2=–11.3 mV, –20.2 mV, –21.4 mV at pHe 6.5, 7.4, 8.5 respectively; the slope factor is 6.2 mV, and is not affected by pHe. Deactivation of i Kr is biexponential, with time constants of the order of 0.5 s and 10 s at –50 mV. Both time constants decrease with external acidification. Also the contribution of the fast component to the total amplitude becomes larger with acidification. Acidification also decreases the fully activated i Kr current. Our experiments demonstrate that extracellular acidification reduces i Kr by increasing the rate of deactivation, causing a shift of the voltage dependence of activation and producing a voltage-dependent block of the fully activated i Kr current.
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