PIP₂ modulation of Slick and Slack K⁺ channels.
Slick and Slack are members of the Slo family of high-conductance potassium channels. These channels are activated by Na(+) and Cl(-) and are highly expressed in the CNS, where they are believed to contribute to the resting membrane potential of neurons and the control of excitability. Herein, we provide evidence that Slick and Slack channels are regulated by the phosphoinositide PIP(2). Two stereoisomers of PIP(2) were able to exogenously activate Slick and Slack channels expressed in Xenopus oocytes, and in addition, it is shown that Slick and Slack channels are modulated by endogenous PIP(2). The activating effect of PIP(2) appears to occur by direct interaction with lysine 306 in Slick and lysine 339 in Slack, located at the proximal C-termini of both channels. Overall, our data suggest that PIP(2) is an important regulator of Slick and Slack channels, yet it is not involved in the recently described cell volume sensitivity of Slick channels, since mutated PIP(2)-insensitive Slick channels retained their sensitivity to cell volume.
Department of Physiology and Biochemistry, IBHV, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark.
Maria
M
de los Angeles Tejada
Lars Jørn
LJ
Jensen
Dan A
DA
Klaerke
D000595:Amino Acid Sequence; D000818:Animals; D048429:Cell Size; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000235:genetics; D009865:Oocytes; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists* / Q000235:genetics; D000081033:Potassium Channels, Sodium-Activated; D014982:Xenopus laevis
C480494:KCNT2 protein, human; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; C000626167:kcnt1 protein, rat; C060980:phosphatidylinositol 3,4-diphosphate