PIP2 modulation of slick and slack K+ channels

Maria de los Angeles Tejada; Lars Jørn Jensen; Dan Arne Klærke

doi:10.1016/j.bbrc.2012.06.038

PIP₂ modulation of slick and slack K⁺ channels

Maria de los Angeles Tejada, Lars Jørn Jensen, Dan Arne Klærke

10 Citations (Scopus)

4032 Downloads (Pure)

Abstract

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.

Original language	English
Journal	Biochemical and Biophysical Research Communications
Volume	424
Issue number	2
Pages (from-to)	208-213
Number of pages	6
ISSN	0006-291X
DOIs	https://doi.org/10.1016/j.bbrc.2012.06.038
Publication status	Published - 27 Jul 2012

Keywords

Former LIFE faculty

Access to Document

10.1016/j.bbrc.2012.06.038

Tejada et al BBRC 2012Submitted manuscript, 1.12 MB

Cite this

@article{ae31f66e2b8b4ba6a59cf0c789a25227,

title = "PIP2 modulation of slick and slack K+ channels",

abstract = "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.",

keywords = "Former LIFE faculty, Slick (Slo2.1), Slack (Slo2.2), Cell volume regulation, Phosphoinositides",

author = "Tejada, {Maria de los Angeles} and Jensen, {Lars J{\o}rn} and Kl{\ae}rke, {Dan Arne}",

year = "2012",

month = jul,

day = "27",

doi = "10.1016/j.bbrc.2012.06.038",

language = "English",

volume = "424",

pages = "208--213",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - PIP2 modulation of slick and slack K+ channels

AU - Tejada, Maria de los Angeles

AU - Jensen, Lars Jørn

AU - Klærke, Dan Arne

PY - 2012/7/27

Y1 - 2012/7/27

N2 - 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.

AB - 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.

KW - Former LIFE faculty

KW - Slick (Slo2.1)

KW - Slack (Slo2.2)

KW - Cell volume regulation

KW - Phosphoinositides

U2 - 10.1016/j.bbrc.2012.06.038

DO - 10.1016/j.bbrc.2012.06.038

M3 - Journal article

C2 - 22728883

SN - 0006-291X

VL - 424

SP - 208

EP - 213

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -