Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations.

Abstract This work demonstrates that extracellular Na + modulates the cloned inwardly rectifying K + channels Kir4.1 and Kir4.1-Kir5.1. Whole-cell patch clamp studies on astrocytes have previously indicated that inward potassium currents are regulated by external Na + . We expressed Kir4.1 and Kir4.1-Kir5.1 in Xenopus oocytes to disclose if Kir4.1 and/or Kir4.1-Kir5.1 at the molecular level are responsible for the observed effect of [Na + ] o and to investigate the regulatory mechanism of external cations further. Our results showed that Na + has a biphasic modulatory effect on both Kir4.1 and Kir4.1-Kir5.1 currents. Depending on the Na + -concentration and applied voltage, the inward Kir4.1/Kir4.1-Kir5.1 currents are either enhanced or reduced by extracellular Na + . The Na + activation was voltage-independent, whereas the Na + -induced reduction of the Kir4.1 and Kir4.1-Kir5.1 currents was both concentration-, time- and voltage-dependent. Our data indicate that the biphasic effect of extracellular Na + on the Kir4.1 and Kir4.1-Kir5.1 channels is caused by two separate mechanisms.