A molecular framework for temperature-dependent gating of ion channels

Sandipan Chowdhury; Brian W Jarecki; Baron Chanda

doi:10.1016/j.cell.2014.07.026

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A molecular framework for temperature-dependent gating of ion channels

Journal article

Open access

Peer reviewed

A molecular framework for temperature-dependent gating of ion channels

Sandipan Chowdhury, Brian W Jarecki and Baron Chanda

Cell, Vol.158(5), pp.1148-1158

08/28/2014

DOI: 10.1016/j.cell.2014.07.026

PMCID: PMC4405168

PMID: 25156949

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https://doi.org/10.1016/j.cell.2014.07.026View

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Abstract

Perception of heat or cold in higher organisms is mediated by specialized ion channels whose gating is exquisitely sensitive to temperature. The physicochemical underpinnings of this temperature-sensitive gating have proven difficult to parse. Here, we took a bottom-up protein design approach and rationally engineered ion channels to activate in response to thermal stimuli. By varying amino acid polarities at sites undergoing state-dependent changes in solvation, we were able to systematically confer temperature sensitivity to a canonical voltage-gated ion channel. Our results imply that the specific heat capacity change during channel gating is a major determinant of thermosensitive gating. We also show that reduction of gating charges amplifies temperature sensitivity of designer channels, which accounts for low-voltage sensitivity in all known temperature-gated ion channels. These emerging principles suggest a plausible molecular mechanism for temperature-dependent gating that reconcile how ion channels with an overall conserved transmembrane architecture may exhibit a wide range of temperature-sensing phenotypes. :

Animals

Humans

Hydrophobic and Hydrophilic Interactions

Ion Channels - chemistry

Ion Channels - metabolism

Models, Molecular

Protein Engineering

Rats

Temperature

Thermodynamics

Details

Title: Subtitle: A molecular framework for temperature-dependent gating of ion channels
Creators: Sandipan Chowdhury - University of Wisconsin–Madison
Brian W Jarecki - University of Wisconsin–Madison
Baron Chanda - University of Wisconsin–Madison
Resource Type: Journal article
Publication Details: Cell, Vol.158(5), pp.1148-1158
DOI: 10.1016/j.cell.2014.07.026
PMID: 25156949
PMCID: PMC4405168
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: R01 NS081293 / NINDS NIH HHS 5T32HL007936-09 / NHLBI NIH HHS T32 HL007936 / NHLBI NIH HHS R01-NS081293 / NINDS NIH HHS
Language: English
Date published: 08/28/2014
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984297607202771

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