The phosphoinositide sensitivity of the K V channel family

Recently, we screened several KV channels for possible dependence on plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2). The channels were expressed in tsA-201 cells and the PI(4,5)P 2 was depleted by several manipulations in whole-cell experiments with parallel measurements of channel activity. In contrast to reports on excised-patches using Xenopus laevis oocytes, we found only KV 7, but none of the other tested KV channels, to be strongly dependent on PI(4,5)P 2. We now have extended our study to KV 1.2 channels, a KV channel we had not previously tested, because a new published study on excised patches showed regulation of the voltage-dependence of activation by PI(4,5)P 2. In full agreement with those published results, we found a reduction of current amplitude by ~20% after depletion of PI(4,5)P 2 and a small left shift in the activation curve of KV 1.2 channels. We also found a small reduction of KV 11.1 (hERG) currents that was not accompanied by a gating shift. In conclusion, our whole-cell methods yield a PI(4,5)P 2-dependence of KV 1.2 currents in tsA-201 cells that is comparable to findings from excised patches of Xenopus laevis oocytes. We discuss possible physiological rationales for PI(4,5)P 2 sensitivity of some ion channels and insensitivity of others.