Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol

Jens A Lundbaek; Pia Birn; Anker J Hansen; Rikke Søgaard; Claus Nielsen; Jeffrey Girshman; Michael J Bruno; Sonya E Tape; Jan Egebjerg; Denise V Greathouse; Gwendolyn L Mattice; Roger E Koeppe; Olaf S Andersen

doi:10.1085/jgp.200308996

Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol

Jens A Lundbaek, Pia Birn, Anker J Hansen, Rikke Søgaard, Claus Nielsen, Jeffrey Girshman, Michael J Bruno, Sonya E Tape, Jan Egebjerg, Denise V Greathouse, Gwendolyn L Mattice, Roger E Koeppe, Olaf S Andersen

ICMM Section 8

182 Citations (Scopus)

Abstract

Membrane proteins are regulated by the lipid bilayer composition. Specific lipid-protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel-bilayer hydrophobic interactions link a "conformational" change (the monomerdimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (beta-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less "stiff", as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer-protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.

Original language	English
Journal	Journal of General Physiology
Volume	123
Issue number	5
Pages (from-to)	599-621
Number of pages	23
ISSN	0022-1295
DOIs	https://doi.org/10.1085/jgp.200308996
Publication status	Published - May 2004

Keywords

Adaptation, Physiological
Cell Line
Cell Membrane
Cholesterol
Elasticity
Gramicidin
Humans
Hydrophobic and Hydrophilic Interactions
Kidney
Lipid Bilayers
Mechanotransduction, Cellular
Membrane Fluidity
Membrane Potentials
Micelles
Sodium Channels
Surface-Active Agents

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10.1085/jgp.200308996

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Lundbaek, J. A., Birn, P., Hansen, A. J., Søgaard, R., Nielsen, C., Girshman, J., Bruno, M. J., Tape, S. E., Egebjerg, J., Greathouse, D. V., Mattice, G. L., Koeppe, R. E., & Andersen, O. S. (2004). Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol. Journal of General Physiology, 123(5), 599-621. https://doi.org/10.1085/jgp.200308996

Regulation of sodium channel function by bilayer elasticity : the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol. / Lundbaek, Jens A; Birn, Pia; Hansen, Anker J et al.

In: Journal of General Physiology, Vol. 123, No. 5, 05.2004, p. 599-621.

Research output: Contribution to journal › Journal article › Research › peer-review

Lundbaek, JA, Birn, P, Hansen, AJ, Søgaard, R, Nielsen, C, Girshman, J, Bruno, MJ, Tape, SE, Egebjerg, J, Greathouse, DV, Mattice, GL, Koeppe, RE & Andersen, OS 2004, 'Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol', Journal of General Physiology, vol. 123, no. 5, pp. 599-621. https://doi.org/10.1085/jgp.200308996

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title = "Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol",

abstract = "Membrane proteins are regulated by the lipid bilayer composition. Specific lipid-protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel-bilayer hydrophobic interactions link a {"}conformational{"} change (the monomerdimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (beta-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less {"}stiff{"}, as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer-protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.",

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T2 - the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol

AU - Lundbaek, Jens A

AU - Birn, Pia

AU - Hansen, Anker J

AU - Søgaard, Rikke

AU - Nielsen, Claus

AU - Girshman, Jeffrey

AU - Bruno, Michael J

AU - Tape, Sonya E

AU - Egebjerg, Jan

AU - Greathouse, Denise V

AU - Mattice, Gwendolyn L

AU - Koeppe, Roger E

AU - Andersen, Olaf S

PY - 2004/5

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N2 - Membrane proteins are regulated by the lipid bilayer composition. Specific lipid-protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel-bilayer hydrophobic interactions link a "conformational" change (the monomerdimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (beta-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less "stiff", as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer-protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.

AB - Membrane proteins are regulated by the lipid bilayer composition. Specific lipid-protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel-bilayer hydrophobic interactions link a "conformational" change (the monomerdimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (beta-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less "stiff", as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer-protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.

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KW - Cholesterol

KW - Elasticity

KW - Gramicidin

KW - Humans

KW - Hydrophobic and Hydrophilic Interactions

KW - Kidney

KW - Lipid Bilayers

KW - Mechanotransduction, Cellular

KW - Membrane Fluidity

KW - Membrane Potentials

KW - Micelles

KW - Sodium Channels

KW - Surface-Active Agents

U2 - 10.1085/jgp.200308996

DO - 10.1085/jgp.200308996

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C2 - 15111647

SN - 0022-1295

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EP - 621

JO - Journal of General Physiology

JF - Journal of General Physiology

IS - 5

ER -

Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol

Abstract

Keywords

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