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Correction: S1-S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation.

Groome JR, Winston V - J. Gen. Physiol. (2015)

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In our 2013 paper in the Journal, we investigated the effects of mutations in the S1, S2, and S3 segments for each of the four domains of the voltage-gated sodium channel of skeletal muscle... As part of that work, we reported the effects of mutations on activation using I-V relations from experiments using the nonpermeant cation N-methyl-d-glucamine for internal and external recording solutions... The corrected parameters for activation of wild-type hNaV1.4 in Table 3 are comparable to conductance measurements for the skeletal muscle sodium channel in other reports... Calculations of the change in free energy associated with activation of hNaV1.4 yielded values of 2–3 kcal/mol for several mutations in the ENC and HCR of domains I–III, and the INC of domains I and II... These values are similar to those calculated for S1 and S2 countercharge mutations in NachBac... Our calculations of free energy differences are based on the effects of point mutations in a single domain of the skeletal muscle sodium channel, and interpretation of the role of S1–S3 countercharges based on those calculations should be limited... In our original paper we concluded that negative countercharges in domains I–III are an important determinant of channel activation, most likely interacting with S4 positively charged residues to facilitate the outward movement of the voltage sensors in those domains in response to membrane depolarization... In addition, we speculated that ENC and HCR countercharge residues in domains I and II may interact with outer positive charges in the S4 segments of these domains... A more recent study does show that ENC residues in domains I and II of rNaV1.4 are important for channel activation... Future work describing the role of HCR or INC residues in activation is also needed to investigate the mechanisms by which S1–S3 countercharges affect sodium channel gating.

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Biophysical characterization of INC mutations. (A) Sodium currents in response to command depolarization to voltages from −90 to 60 mV. Effects of INC mutations are shown for activation (B), steady-state fast inactivation (C), entry into fast inactivation (D and E), and recovery (F and G). Legends identify residues and locus by domain and segment. Values represent mean ± SEM (error bars) from 10–23 experiments. The additional panel (H) is shown for g-V relations for hNaV1.4 and mutations of the INC in domains I and II. Boltzmann fits to each plot are shown by dotted lines.
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fig10: Biophysical characterization of INC mutations. (A) Sodium currents in response to command depolarization to voltages from −90 to 60 mV. Effects of INC mutations are shown for activation (B), steady-state fast inactivation (C), entry into fast inactivation (D and E), and recovery (F and G). Legends identify residues and locus by domain and segment. Values represent mean ± SEM (error bars) from 10–23 experiments. The additional panel (H) is shown for g-V relations for hNaV1.4 and mutations of the INC in domains I and II. Boltzmann fits to each plot are shown by dotted lines.

Mentions: These conditions do not provide a measure of driving force as needed for a Boltzmann fit to obtain conductance parameters of midpoint and slope factor. Therefore, we have analyzed the original dataset using the asymptote for the relative change in current amplitude to estimate driving force and plot G-V relations. G/GMAX was plotted as a function of voltage, and these curves were fit with a Boltzmann function to yield corrected values for midpoint and slope factor. These values and calculations for the change in free energy (ΔΔGo, nzFV0.5) for mutations are provided in Table 3. Correction to plots for I-V relations given in the original paper are provided as extra panels for Figs. 2, 6, and 10. Fig. 11 has been replotted in its entirety. Table 3 and Figs. 2, 6, 10, and 11 are below.


Correction: S1-S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation.

Groome JR, Winston V - J. Gen. Physiol. (2015)

Biophysical characterization of INC mutations. (A) Sodium currents in response to command depolarization to voltages from −90 to 60 mV. Effects of INC mutations are shown for activation (B), steady-state fast inactivation (C), entry into fast inactivation (D and E), and recovery (F and G). Legends identify residues and locus by domain and segment. Values represent mean ± SEM (error bars) from 10–23 experiments. The additional panel (H) is shown for g-V relations for hNaV1.4 and mutations of the INC in domains I and II. Boltzmann fits to each plot are shown by dotted lines.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4664822&req=5

fig10: Biophysical characterization of INC mutations. (A) Sodium currents in response to command depolarization to voltages from −90 to 60 mV. Effects of INC mutations are shown for activation (B), steady-state fast inactivation (C), entry into fast inactivation (D and E), and recovery (F and G). Legends identify residues and locus by domain and segment. Values represent mean ± SEM (error bars) from 10–23 experiments. The additional panel (H) is shown for g-V relations for hNaV1.4 and mutations of the INC in domains I and II. Boltzmann fits to each plot are shown by dotted lines.
Mentions: These conditions do not provide a measure of driving force as needed for a Boltzmann fit to obtain conductance parameters of midpoint and slope factor. Therefore, we have analyzed the original dataset using the asymptote for the relative change in current amplitude to estimate driving force and plot G-V relations. G/GMAX was plotted as a function of voltage, and these curves were fit with a Boltzmann function to yield corrected values for midpoint and slope factor. These values and calculations for the change in free energy (ΔΔGo, nzFV0.5) for mutations are provided in Table 3. Correction to plots for I-V relations given in the original paper are provided as extra panels for Figs. 2, 6, and 10. Fig. 11 has been replotted in its entirety. Table 3 and Figs. 2, 6, 10, and 11 are below.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

In our 2013 paper in the Journal, we investigated the effects of mutations in the S1, S2, and S3 segments for each of the four domains of the voltage-gated sodium channel of skeletal muscle... As part of that work, we reported the effects of mutations on activation using I-V relations from experiments using the nonpermeant cation N-methyl-d-glucamine for internal and external recording solutions... The corrected parameters for activation of wild-type hNaV1.4 in Table 3 are comparable to conductance measurements for the skeletal muscle sodium channel in other reports... Calculations of the change in free energy associated with activation of hNaV1.4 yielded values of 2–3 kcal/mol for several mutations in the ENC and HCR of domains I–III, and the INC of domains I and II... These values are similar to those calculated for S1 and S2 countercharge mutations in NachBac... Our calculations of free energy differences are based on the effects of point mutations in a single domain of the skeletal muscle sodium channel, and interpretation of the role of S1–S3 countercharges based on those calculations should be limited... In our original paper we concluded that negative countercharges in domains I–III are an important determinant of channel activation, most likely interacting with S4 positively charged residues to facilitate the outward movement of the voltage sensors in those domains in response to membrane depolarization... In addition, we speculated that ENC and HCR countercharge residues in domains I and II may interact with outer positive charges in the S4 segments of these domains... A more recent study does show that ENC residues in domains I and II of rNaV1.4 are important for channel activation... Future work describing the role of HCR or INC residues in activation is also needed to investigate the mechanisms by which S1–S3 countercharges affect sodium channel gating.

No MeSH data available.


Related in: MedlinePlus