Differential effects of paramyotonia congenita mutations F1473S and F1705I on sodium channel gating.

Abstract

We investigated effects of paramyotonia congenita mutations F1473S and F1705I on gating of skeletal muscle Na+ channels. We used on-cell recordings from Xenopus oocytes to compare fast inactivation and deactivation in wild-type and mutant channels. Then, we used gating current recordings to determine how these actions of PC mutants might be reflected in their effects on charge movement and its immobilization. F1473S, but not F1705I, accelerated deactivation from the inactivated state and enhanced the remobilization of gating charge. F1473S and F1705I decreased the completion of closed-state fast inactivation, and decreased charge movement over the voltage range at which channels did not activate. An unexpected result was that F1705I increased the extent of charge immobilization in response to strong depolarization. Our results suggest that the DIV S4-S5 linker mutation F1473S promotes the hyperpolarized position of DIVS4 to accelerate recovery. Inhibition of charge movement by F1473S and F1705I in the absence of channel opening is discussed with respect to their effects on closed-state fast inactivation.

• Authors: James R Groome, Matthew F Larsen, Allyson Coonts
• Journal: Channels (Austin, Tex.) (Channels (Austin)) 2008 Jan-Feb Vol. 2 Issue 1 Pg. 39-50 ISSN: 1933-6969 [Electronic] United States
• PMID: 18690054 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• NAV1.4 Voltage-Gated Sodium Channel
• SCN4A protein, human
• Sodium Channels

Topics

• Animals
• Electrophysiology (methods)
• Humans
• Ion Channel Gating
• Kinetics
• Muscle, Skeletal (metabolism)
• Mutagenesis, Site-Directed
• Mutation
• Myotonic Disorders (genetics)
• NAV1.4 Voltage-Gated Sodium Channel
• Oocytes (metabolism)
• Patch-Clamp Techniques
• Phenotype
• Sodium Channels (chemistry, genetics)
• Xenopus laevis