Vereecke J, Carmeliet E
Laboratorium voor Fysiologie, Leuven, Belgium.
Pflugers Arch. 2000 Apr;439(6):739-51. doi: 10.1007/s004249900243.
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.
采用全细胞钳技术研究细胞外pH值（pHe）对兔心室肌细胞延迟整流钾电流iKr的影响。由于已有多种关于pH值对表达的hERG通道影响的报道，我们的目的是研究pH值对天然环境中iKr通道的影响。细胞外酸化会使iKr降低，且其失活更快。细胞外酸化导致稳态激活曲线明显向更正电位偏移，而碱化则不会产生明显偏移。在pHe为6.5、7.4、8.5时，E1/2分别为-11.3 mV、-20.2 mV、-21.4 mV；斜率因子为6.2 mV，不受pHe影响。iKr的失活是双指数的，在-50 mV时时间常数约为0.5 s和10 s。两个时间常数都随细胞外酸化而减小。而且快速成分对总幅度的贡献也随着酸化而变大。酸化还会降低完全激活的iKr电流。我们的实验表明，细胞外酸化通过增加失活速率、导致激活的电压依赖性发生偏移以及对完全激活的iKr电流产生电压依赖性阻滞来降低iKr。
