Department of Physiology and Biochemistry, IBHV, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark.
Biochem Biophys Res Commun. 2012 Jul 27;424(2):208-13. doi: 10.1016/j.bbrc.2012.06.038. Epub 2012 Jun 21.
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.
Slick 和 Slack 是高电导钾通道 Slo 家族的成员。这些通道被 Na(+) 和 Cl(-) 激活，在中枢神经系统中高度表达，据信它们有助于神经元的静息膜电位和兴奋性的控制。在此，我们提供证据表明 Slick 和 Slack 通道受磷酸肌醇 PIP(2)调节。两种 PIP(2)立体异构体能够体外激活在非洲爪蟾卵母细胞中表达的 Slick 和 Slack 通道，此外，还表明 Slick 和 Slack 通道受内源性 PIP(2)调节。PIP(2)的激活作用似乎通过与 Slick 中的赖氨酸 306 和 Slack 中的赖氨酸 339 直接相互作用发生，这两个残基位于两个通道的近端 C 末端。总的来说，我们的数据表明 PIP(2)是 Slick 和 Slack 通道的重要调节剂，但它不参与最近描述的 Slick 通道的细胞体积敏感性，因为突变的 PIP(2)不敏感的 Slick 通道仍然对细胞体积敏感。
