Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations.
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.
Søe
Rikke
R
Department of Physiology and Biochemistry, IBHV, Faculty of Life Sciences, University of Copenhagen. Grønnegaardsvej 7, 1870 Frederiksberg C, Denmark. rso@life.ku.dk
Andreasen
Mogens
M
Klaerke
Dan Arne
DA
D000818:Animals; D002412:Cations / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D055503:Protein Multimerization / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D014982:Xenopus laevis; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel
D002412:Cations; D008094:Lithium; D024661:Potassium Channels, Inwardly Rectifying; D012964:Sodium; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel