A conserved glutamate is important for slow inactivation in K+ channels

Hans P Larsson, Fredrik Elinder

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfidelinking 418C to two different cysteines, introduced in the Pore-S6(P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.

Original languageEnglish
Pages (from-to)573-583
Number of pages11
JournalNeuron
Volume27
Issue number3
StatePublished - Dec 7 2000
Externally publishedYes

Fingerprint

S 6
Glutamic Acid
Cysteine
Ion Channels
Hydrogen

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A conserved glutamate is important for slow inactivation in K+ channels. / Larsson, Hans P; Elinder, Fredrik.

In: Neuron, Vol. 27, No. 3, 07.12.2000, p. 573-583.

Research output: Contribution to journalArticle

Larsson, Hans P ; Elinder, Fredrik. / A conserved glutamate is important for slow inactivation in K+ channels. In: Neuron. 2000 ; Vol. 27, No. 3. pp. 573-583.
@article{7b8ef7c6b109424aa83336a0721aae2b,
title = "A conserved glutamate is important for slow inactivation in K+ channels",
abstract = "Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfidelinking 418C to two different cysteines, introduced in the Pore-S6(P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.",
author = "Larsson, {Hans P} and Fredrik Elinder",
year = "2000",
month = "12",
day = "7",
language = "English",
volume = "27",
pages = "573--583",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - A conserved glutamate is important for slow inactivation in K+ channels

AU - Larsson, Hans P

AU - Elinder, Fredrik

PY - 2000/12/7

Y1 - 2000/12/7

N2 - Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfidelinking 418C to two different cysteines, introduced in the Pore-S6(P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.

AB - Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfidelinking 418C to two different cysteines, introduced in the Pore-S6(P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.

UR - http://www.scopus.com/inward/record.url?scp=0033681165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033681165&partnerID=8YFLogxK

M3 - Article

VL - 27

SP - 573

EP - 583

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 3

ER -