Activation-coupled inactivation in the bacterial potassium channel KcsA

Lizhi Gao, Xianqiang Mi, Vesa Paajanen, Kun Wang, Zheng Fan

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

X-ray structures of the bacterial K+ channel KcsA have led to unparalleled progress in our understanding of ion channel structures. The KcsA channel has therefore been a prototypic model used to study the structural basis of ion channel function, including the gating mechanism. This channel was previously found to close at near-neutral intracellular pH (pHi) and to open at acidic pHi. Here, we report the presence of a previously unknown channel inactivation process that occurs after the KcsA channel is activated. In our experiments, mammalian cells transfected with a codon-optimized synthetic gene encoding the KcsA protein expressed K +-selective channels that activated in response to a decrease in pHi. Using patch-clamp and rapid solution exchange techniques, we observed that the KcsA channels inactivated within hundreds of milliseconds after channel activation. At all tested pHs, inactivation always accompanied activation, and it was profoundly accelerated in the same pH range at which activation increased steeply. Recovery from inactivation was observed, and its extent depended on the pHi and the amount of time that the channel was inactive. KcsA channel inactivation can be described by a kinetic model in which pHi controls inactivation through pH-dependent activation. This heretofore-undocumented inactivation process increases the complexity of KcsA channel function, but it also offers a potential model for studying the structural correspondence of ion channel inactivation.

Original languageEnglish (US)
Pages (from-to)17630-17635
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number49
DOIs
StatePublished - Dec 6 2005

Fingerprint

Potassium Channels
Ion Channels
Synthetic Genes
Bacterial Structures
Structural Models
Codon
X-Rays

All Science Journal Classification (ASJC) codes

  • General

Cite this

Activation-coupled inactivation in the bacterial potassium channel KcsA. / Gao, Lizhi; Mi, Xianqiang; Paajanen, Vesa; Wang, Kun; Fan, Zheng.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 49, 06.12.2005, p. 17630-17635.

Research output: Contribution to journalArticle

@article{8796135d9ec44607b169dccbf1e766be,
title = "Activation-coupled inactivation in the bacterial potassium channel KcsA",
abstract = "X-ray structures of the bacterial K+ channel KcsA have led to unparalleled progress in our understanding of ion channel structures. The KcsA channel has therefore been a prototypic model used to study the structural basis of ion channel function, including the gating mechanism. This channel was previously found to close at near-neutral intracellular pH (pHi) and to open at acidic pHi. Here, we report the presence of a previously unknown channel inactivation process that occurs after the KcsA channel is activated. In our experiments, mammalian cells transfected with a codon-optimized synthetic gene encoding the KcsA protein expressed K +-selective channels that activated in response to a decrease in pHi. Using patch-clamp and rapid solution exchange techniques, we observed that the KcsA channels inactivated within hundreds of milliseconds after channel activation. At all tested pHs, inactivation always accompanied activation, and it was profoundly accelerated in the same pH range at which activation increased steeply. Recovery from inactivation was observed, and its extent depended on the pHi and the amount of time that the channel was inactive. KcsA channel inactivation can be described by a kinetic model in which pHi controls inactivation through pH-dependent activation. This heretofore-undocumented inactivation process increases the complexity of KcsA channel function, but it also offers a potential model for studying the structural correspondence of ion channel inactivation.",
author = "Lizhi Gao and Xianqiang Mi and Vesa Paajanen and Kun Wang and Zheng Fan",
year = "2005",
month = "12",
day = "6",
doi = "10.1073/pnas.0505158102",
language = "English (US)",
volume = "102",
pages = "17630--17635",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "49",

}

TY - JOUR

T1 - Activation-coupled inactivation in the bacterial potassium channel KcsA

AU - Gao, Lizhi

AU - Mi, Xianqiang

AU - Paajanen, Vesa

AU - Wang, Kun

AU - Fan, Zheng

PY - 2005/12/6

Y1 - 2005/12/6

N2 - X-ray structures of the bacterial K+ channel KcsA have led to unparalleled progress in our understanding of ion channel structures. The KcsA channel has therefore been a prototypic model used to study the structural basis of ion channel function, including the gating mechanism. This channel was previously found to close at near-neutral intracellular pH (pHi) and to open at acidic pHi. Here, we report the presence of a previously unknown channel inactivation process that occurs after the KcsA channel is activated. In our experiments, mammalian cells transfected with a codon-optimized synthetic gene encoding the KcsA protein expressed K +-selective channels that activated in response to a decrease in pHi. Using patch-clamp and rapid solution exchange techniques, we observed that the KcsA channels inactivated within hundreds of milliseconds after channel activation. At all tested pHs, inactivation always accompanied activation, and it was profoundly accelerated in the same pH range at which activation increased steeply. Recovery from inactivation was observed, and its extent depended on the pHi and the amount of time that the channel was inactive. KcsA channel inactivation can be described by a kinetic model in which pHi controls inactivation through pH-dependent activation. This heretofore-undocumented inactivation process increases the complexity of KcsA channel function, but it also offers a potential model for studying the structural correspondence of ion channel inactivation.

AB - X-ray structures of the bacterial K+ channel KcsA have led to unparalleled progress in our understanding of ion channel structures. The KcsA channel has therefore been a prototypic model used to study the structural basis of ion channel function, including the gating mechanism. This channel was previously found to close at near-neutral intracellular pH (pHi) and to open at acidic pHi. Here, we report the presence of a previously unknown channel inactivation process that occurs after the KcsA channel is activated. In our experiments, mammalian cells transfected with a codon-optimized synthetic gene encoding the KcsA protein expressed K +-selective channels that activated in response to a decrease in pHi. Using patch-clamp and rapid solution exchange techniques, we observed that the KcsA channels inactivated within hundreds of milliseconds after channel activation. At all tested pHs, inactivation always accompanied activation, and it was profoundly accelerated in the same pH range at which activation increased steeply. Recovery from inactivation was observed, and its extent depended on the pHi and the amount of time that the channel was inactive. KcsA channel inactivation can be described by a kinetic model in which pHi controls inactivation through pH-dependent activation. This heretofore-undocumented inactivation process increases the complexity of KcsA channel function, but it also offers a potential model for studying the structural correspondence of ion channel inactivation.

UR - http://www.scopus.com/inward/record.url?scp=29144472228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29144472228&partnerID=8YFLogxK

U2 - 10.1073/pnas.0505158102

DO - 10.1073/pnas.0505158102

M3 - Article

VL - 102

SP - 17630

EP - 17635

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 49

ER -