Slow inactivation of voltage gated ion channels

电压门控离子通道，特别是钠、钾和钙通道，以及其他类型的通道有几个共同的特征，特别是缓慢的失活，这一过程在分子水平上还没有被很好地理解。几年前，这个实验室发现，细胞内pH的变化会使鱿鱼巨型轴突中的K通道失活发生电压漂移，特别是在6和10的pH范围内，单位pH变化导致电压轴上失活曲线的中点移动10 mV。在非洲爪哇卵母细胞中异源表达的Shaker K通道没有类似的结果。初步结果表明，尽管Shaker K通道的缓慢失活与Squid K通道的缓慢失活非常相似，但该效应并不存在。使用两个异源表达的通道的定点突变对pH影响的比较分析，应该会对缓慢失活机制产生重要的洞察力。

Voltage-gated ion channels, specifically Na, K, and Ca channels, as well as other channel types share several features in common, in particular slow inactivation, a process that is not well understood at the molecular level. Several years ago, this laboratory discovered that K channel inactivation in squid giant axons was voltage-shifted by changes in the intracellular pH, specifically a 10 mV shift in the midpoint of the inactiavtion curve on the voltage axis per unit pH change in the 6 < pH < 10 range. A similar result has not been reported for the Shaker K channel expressed heterologously in Xenopus oocytes. Preliminary results have suggested the absence of this effect, even though slow inactivation of the Shaker K channel is remarkably similar to that of the squid K channel. A comparative analysis of the pH effect using site-directed mutagenesis of both channels, each heterologously expressed, should yield significant insight into the slow inactivation mechanism.