Molecular basis of ion permeability in a voltage‐gated sodium channel

Naylor, C.E.; Bagnéris, Claire; DeCaen, Paul G.; Sula, Altin; Scaglione, Antonella; Clapham, David E.; Wallace, B.A.

doi:10.15252/embj.201593285

Cited by 100 publications

(145 citation statements)

References 50 publications

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“…These results for LESWAS and LEDWAS channels are consistent with previous reports [4,6,32]. The LEDWAS mutant contains a doubly-charged ring {EEEE+DDDD} locus instead of the singly charged ring {EEEE} locus of LESWAS but it was shown earlier [10] that the conduction bands are insensitive to the spatial distribution of charge along the SF.…”

Section: Site Directed Mutagenesis/patch Clamp Studies Of Nachbac Chasupporting

confidence: 91%

“…Equation (6) and the phase diagram provide a simple and transparent explanation of the simulation results. The origin of the shift lies in the logarithmic concentration dependence of DM n in equation (6). Similar shifts were seen in earlier simulations [15].…”

Section: Phase Transition Diagramssupporting

confidence: 85%

“…2 and 3) are in reasonable agreement with the ICB model, though the Q f values for the resonant points M n differ from the exact predictions of equation (6). This is because of singular ionion interactions that are not taken account of in the ICB model, and because of possible electric field leaks due to the finite length of the SF.…”

Section: Ionic Coulomb Blockade and Concentrationrelated Shiftmentioning

confidence: 72%

“…It is known, however, that the conduction and selectivity properties of cation channels are defined by the ions' movements and interactions inside a short, narrow selectivity filter (SF) lined by negatively charged amino acid residues that provide a net fixed charge Q f [1,2]. NaChBac bacterial sodium channels [4][5][6][7] are frequently thought of, and used as, simplified experimental/ simulation models of mammalian calcium and sodium channels. X-ray investigations and molecular dynamics simulations have shown that these tetrameric channels possess strong binding sites with 4-glutamate {EEEE} loci at the SF [8].…”

Section: Introductionmentioning

confidence: 99%

“…X-ray investigations and molecular dynamics simulations have shown that these tetrameric channels possess strong binding sites with 4-glutamate {EEEE} loci at the SF [8]. Bacterial channels have been used in sitedirected mutagenesis (SDM)/patch clamp studies of conductivity and selectivity [6,9].…”

Section: Introductionmentioning

confidence: 99%

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Ionic Coulomb blockade and anomalous mole fraction effect in the NaChBac bacterial ion channel and its charge-varied mutants

Kaufman¹,

Fedorenko²,

Luchinsky³

et al. 2017

EPJ Nonlinear Biomed. Phys.

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Abstract. Background. The selectivity of biological cation channels is defined by a short, narrow selectivity filter, having a negative net fixed charge Q f . Voltage gated bacterial channels (NaChBac and some others) are frequently used in biophysics as simplified models of mammalian calcium and sodium channels. We report an experimental, analytic and numerical study of the effects of Q f and bulk ionic concentrations of Ca 2+ and Na + on conduction and selectivity of NaChBac channels, wild type and Q f -varied mutants. Methods. Site-directed mutagenesis and voltage clamp recordings were used to investigate the Na + /Ca 2+ selectivity, divalent blockade and anomalous mole fraction effect (AMFE) for different NaChBac wild type/ mutants channels and the properties dependence on Q f . Experimental results were compared with Brownian dynamics simulations and with analytic predictions of the ionic Coulomb blockade (ICB) model, which was extended to encompass bulk concentration effects. Results. It was shown that changing of Q f from -4e (for LESWAS wild type) to -8e (for LEDWAS mutant) leads to strong divalent blockade of the Na + current by micromolar amounts of Ca 2+ ions, similar to the effects seen in mammalian calcium channels. The BD simulations revealed a concentration-related logarithmic shift of the conduction bands. These results were shown to be consistent with ICB model predictions. Conclusions. The extended ICB model explains the experimental (divalent blockade and AMFE) and simulated (multi-ion bands and their concentration-related shifts) selectivity phenomena of NaChBac channel and its charge-varied mutants. These results extend the understanding of ion channel selectivity and may also be applicable to biomimetic nanopores with charged walls.

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Section: Site Directed Mutagenesis/patch Clamp Studies Of Nachbac Chasupporting

confidence: 91%

Section: Phase Transition Diagramssupporting

confidence: 85%

Section: Ionic Coulomb Blockade and Concentrationrelated Shiftmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ionic Coulomb blockade and anomalous mole fraction effect in the NaChBac bacterial ion channel and its charge-varied mutants

Kaufman¹,

Fedorenko²,

Luchinsky³

et al. 2017

EPJ Nonlinear Biomed. Phys.

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Optimized expression and purification of NavAb provide the structural insight into the voltage dependence

et al. 2018

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Voltage-gated sodium channels are crucial for electro-signalling in living systems. Analysis of the molecular mechanism requires both fine electrophysiological evaluation and high-resolution channel structures. Here, we optimized a dual expression system of NavAb, which is a well-established standard of prokaryotic voltage-gated sodium channels, for E. coli and insect cells using a single plasmid vector to analyse high-resolution protein structures and measure large ionic currents. Using this expression system, we evaluated the voltage dependence and determined the crystal structures of NavAb wild-type and two mutants, E32Q and N49K, whose voltage dependence were positively shifted and essential interactions were lost in voltage sensor domain. The structural and functional comparison elucidated the molecular mechanisms of the voltage dependence of prokaryotic voltage-gated sodium channels.

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Sulfur‐Containing Foldamer‐Based Artificial Lithium Channels

Shen

Deepa

et al. 2023

Angewandte Chemie

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Unlike many other biologically relevant ions (Na+, K+, Ca2+, Cl‐, etc) and protons, whose cellular concentrations are closely regulated by highly selective channel proteins, Li+ ion is unusual in that its concentration is well tolerated over many orders of magnitude and that no lithium‐specific channel proteins have so far been identified. While one naturally evolved primary pathway for lithium ions to traverse across the cell membrane is through sodium channels by competing with sodium ions, highly sought‐after artificial lithium‐transporting channels remain a major challenge to develop. Here we show that sulfur‐containing organic nanotubes derived from intramolecularly H‐bonded helically folded aromatic foldamers of 3.6 Å in hollow cavity diameter could facilitate highly selective and efficient transmembrane transport of Li+ ions, with high transport selectivity factors of 14.9 and 18.4 over Na+ and K+ ions, respectively.

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Molecular basis of ion permeability in a voltage‐gated sodium channel

Cited by 100 publications

References 50 publications

Ionic Coulomb blockade and anomalous mole fraction effect in the NaChBac bacterial ion channel and its charge-varied mutants

Ionic Coulomb blockade and anomalous mole fraction effect in the NaChBac bacterial ion channel and its charge-varied mutants

Optimized expression and purification of NavAb provide the structural insight into the voltage dependence

Sulfur‐Containing Foldamer‐Based Artificial Lithium Channels

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