Sodium Channel Myotonia Due to Novel Mutations in Domain I of Nav1.4

Figures

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  Figure 1. Family trees. (A–F) Family trees of families that carried p.Ile215Thr. In the picture, we indicated by arrows the two probands, IV.2 heterozygote, and IV.4 homozygote for the target mutation. As depicted by the doubled lines, two marriages between relatives occurred in this family, and only one homozygote was generated (*). (G) Family tree of the only family carrying p.Gly241Val.

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  Figure 2. Effects of p.Ile215Thr and p.Gly241Val mutations on Nav1.4 functional properties. (A) Representative traces of whole-cell sodium currents; the arrows indicate the currents in response to the voltage step at −30 mV. Normalized current/voltage relationship was obtained by normalizing current by cell capacitance. Voltage dependence of activation was studied by applying the protocol represented and by fitting the normalized conductance by a Boltzmann curve. Comparison with WT indicates a shift of −10 and −12 mV for the curves of p.Ile215Thr and p.Gly241Val, respectively. (B) Voltage dependence of fast inactivation. A mild shift toward hyperpolarized potentials is observed only for p.Gly241Val. (C) Slow inactivation properties studied with long conditioning voltage pulses. Changes in the V1/2 are observed for both p.Ile215Thr and p.Gly241Val. (D) Window currents obtained overlapping activation and inactivation curves; they identify the voltage range in which Nav1.4 channels are available for opening. p.Ile215Thr and p.Gly241Val show to be available to open in a more hyperpolarized voltage range compared to WT.

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  Figure 3. Traces illustrating the current decay for WT and mutant channels.

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  Figure 4. Curves illustrating the time constants (τ) for WT and mutant channel current decay in the range of potentials from −30 to 10 mV.