August 21, 2012Journal of Biological ChemistryOpen Access

KCNQ1 Channels Do Not Undergo Concerted but Sequential Gating Transitions in Both the Absence and the Presence of KCNE1 Protein

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Population

Concatenated tetrameric KCNQ1 channels (in vitro model)

Comparison

Introduction of R231W and R243W mutations into… vs Wild-type KCNQ1 channels or channels with…

Design

Preclinical

Authors

EMEshcar MeiselTel Aviv University MDMeidan DvirTeva Pharmaceuticals (Israel)YHYoni HaitinTel Aviv University

Discussion

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Implication

Sequential KCNQ1 gating challenges Shaker model; leaves open relevance to human LQT1 before clinical translation.

Structured PICO

Population

Concatenated tetrameric KCNQ1 channels (in vitro model)

Intervention

Introduction of R231W (gain of function) and R243W (loss of function) mutations into the S4 helix of the voltage sensor domain of one, two, three, and four subunits, with and without KCNE1

Comparator

Wild-type KCNQ1 channels or channels with different numbers of mutated subunits

Outcome

Voltage dependence of activation and gating transitions (thermodynamic mutant cycle analysis)surrogate

KCNQ1 channels undergo sequential gating transitions leading to channel opening even before all voltage sensor domains have moved, contrary to the concerted opening seen in Shaker channels.

Cite This Study

Meisel et al. (2012) studied this question.

synapsesocial.com/papers/6a9121fc780df83b8fe1be6c https://doi.org/10.1074/jbc.m112.364901

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KCNQ1 Channels Do Not Undergo Concerted but Sequential Gating Transitions in Both the Absence and the Presence of KCNE1 Protein

Discussion

Member takes

Implication

Structured PICO

Cite This Study

KCNQ1 Channels Do Not Undergo Concerted but Sequential Gating Transitions in Both the Absence and the Presence of KCNE1 Protein

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Also Consider