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Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy

Journal Article


Abstract


  • Striking structural differences between voltage-gated sodium (Nav) channels from prokaryotes (homotetramers)

    and eukaryotes (asymmetric, four-domain proteins) suggest the likelihood of different molecular mechanisms for

    common functions. For these two channel families, our data show similar selectivity sequences among alkali cations

    (relative permeability, Pion/PNa) and asymmetric, bi-ionic reversal potentials when the Na/K gradient is reversed.

    We performed coordinated experimental and computational studies, respectively, on the prokaryotic Nav channels NaChBac and NavAb. NaChBac shows an “anomalous,” nonmonotonic mole-fraction dependence in the presence of certain sodium–potassium mixtures; to our knowledge, no comparable observation has been reported for

    eukaryotic Nav channels. NaChBac’s preferential selectivity for sodium is reduced either by partial titration of its

    highly charged selectivity filter, when extracellular pH is lowered from 7.4 to 5.8, or by perturbation—likely steric—associated with a nominally electro-neutral substitution in the selectivity filter (E191D). Although no single

    molecular feature or energetic parameter appears to dominate, our atomistic simulations, based on the published

    NavAb crystal structure, revealed factors that may contribute to the normally observed selectivity for Na over K.

    These include: (a) a thermodynamic penalty to exchange one K+

    for one Na+

    in the wild-type (WT) channel, increasing the relative likelihood of Na+

    occupying the binding site; (b) a small tendency toward weaker ion binding

    to the selectivity filter in Na–K mixtures, consistent with the higher conductance observed with both sodium and

    potassium present; and (c) integrated 1-D potentials of mean force for sodium or potassium movement that show

    less separation for the less selective E/D mutant than for WT. Overall, tight binding of a single favored ion to the

    selectivity filter, together with crucial inter-ion interactions within the pore, suggests that prokaryotic Nav channels

    use a selective strategy more akin to those of eukaryotic calcium and potassium channels than that of eukaryotic

    Nav channels.

UOW Authors


  •   Finol Urdaneta, Rocio
  •   Wang, Yibo (external author)
  •   Al-Sabi, Ahmed (external author)
  •   Zhao, Chunfeng (external author)
  •   Noskov, Sergei Y. (external author)
  •   French, Robert J. (external author)

Publication Date


  • 2014

Geographic Focus


Citation


  • Finol-Urdaneta, R. K., Wang, Y., Al-Sabi, A., Zhao, C., Noskov, S. Y. & French, R. J. (2014). Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy. Journal of General Physiology, 143 (2), 157-171.

Scopus Eid


  • 2-s2.0-84893077319

Has Global Citation Frequency


Number Of Pages


  • 14

Start Page


  • 157

End Page


  • 171

Volume


  • 143

Issue


  • 2

Place Of Publication


  • United States

Abstract


  • Striking structural differences between voltage-gated sodium (Nav) channels from prokaryotes (homotetramers)

    and eukaryotes (asymmetric, four-domain proteins) suggest the likelihood of different molecular mechanisms for

    common functions. For these two channel families, our data show similar selectivity sequences among alkali cations

    (relative permeability, Pion/PNa) and asymmetric, bi-ionic reversal potentials when the Na/K gradient is reversed.

    We performed coordinated experimental and computational studies, respectively, on the prokaryotic Nav channels NaChBac and NavAb. NaChBac shows an “anomalous,” nonmonotonic mole-fraction dependence in the presence of certain sodium–potassium mixtures; to our knowledge, no comparable observation has been reported for

    eukaryotic Nav channels. NaChBac’s preferential selectivity for sodium is reduced either by partial titration of its

    highly charged selectivity filter, when extracellular pH is lowered from 7.4 to 5.8, or by perturbation—likely steric—associated with a nominally electro-neutral substitution in the selectivity filter (E191D). Although no single

    molecular feature or energetic parameter appears to dominate, our atomistic simulations, based on the published

    NavAb crystal structure, revealed factors that may contribute to the normally observed selectivity for Na over K.

    These include: (a) a thermodynamic penalty to exchange one K+

    for one Na+

    in the wild-type (WT) channel, increasing the relative likelihood of Na+

    occupying the binding site; (b) a small tendency toward weaker ion binding

    to the selectivity filter in Na–K mixtures, consistent with the higher conductance observed with both sodium and

    potassium present; and (c) integrated 1-D potentials of mean force for sodium or potassium movement that show

    less separation for the less selective E/D mutant than for WT. Overall, tight binding of a single favored ion to the

    selectivity filter, together with crucial inter-ion interactions within the pore, suggests that prokaryotic Nav channels

    use a selective strategy more akin to those of eukaryotic calcium and potassium channels than that of eukaryotic

    Nav channels.

UOW Authors


  •   Finol Urdaneta, Rocio
  •   Wang, Yibo (external author)
  •   Al-Sabi, Ahmed (external author)
  •   Zhao, Chunfeng (external author)
  •   Noskov, Sergei Y. (external author)
  •   French, Robert J. (external author)

Publication Date


  • 2014

Geographic Focus


Citation


  • Finol-Urdaneta, R. K., Wang, Y., Al-Sabi, A., Zhao, C., Noskov, S. Y. & French, R. J. (2014). Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy. Journal of General Physiology, 143 (2), 157-171.

Scopus Eid


  • 2-s2.0-84893077319

Has Global Citation Frequency


Number Of Pages


  • 14

Start Page


  • 157

End Page


  • 171

Volume


  • 143

Issue


  • 2

Place Of Publication


  • United States