The effect of external pH on the delayed rectifying K+ current in cardiac ventricular myocytes

The effects of extracellular pH (pHe) on the delayed rectifying K+ current iKr 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 iKr channels in their native environment. iKr 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. E1/2= - 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 iKr 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 iKr current. Our experiments demonstrate that extracellular acidification reduces iKr 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 iKr current.