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Cell. 2014 Aug 28;158(5):1148-1158. doi: 10.1016/j.cell.2014.07.026. Epub 2014 Aug 21.

A molecular framework for temperature-dependent gating of ion channels.

Author information

1
Graduate Program in Biophysics, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA; Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA.
2
Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA.
3
Graduate Program in Biophysics, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA; Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA. Electronic address: chanda@wisc.edu.

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.

PMID:
25156949
PMCID:
PMC4405168
DOI:
10.1016/j.cell.2014.07.026
[Indexed for MEDLINE]
Free PMC Article

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