Abstract
Altered modulation of skeletal muscle voltage-gated sodium channels by myotonic dystrophy kinase (DMPK) has been proposed as a possible mechanism underlying myotonia in this disease. We examined the effect of a recombinant mouse DMPK on the functional properties of human skeletal muscle (hSkM1) and cardiac (hH1) voltage-gated sodium channels in the Xenopus oocyte expression system. Co-expression of DMPK with hSkM1 in oocytes resulted in significantly lower peak sodium current amplitude as compared to cells expressing hSkM1 alone in agreement with a previous report. By contrast, DMPK had no effect on the level of expressed sodium current in cells expressing hH1. Similarly, there mere no measurable effects of the kinase on the kinetics or steady-state properties of activation or inactivation. Our findings support the previous observations made with rat muscle sodium channels and demonstrate that the effect of DMPK on sodium channels is isoform specific despite conservation of a putative phosphorylation site between the two isoforms.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 621-624 |
| Number of pages | 4 |
| Journal | FEBS Letters |
| Volume | 412 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 4 1997 |
Funding
We would like to thank Drs. B. Wieringa for providing the mouse DMPK cDNA, and J.R. Moorman for helpful discussion. This work was supported by grants from the National Institutes of Health (NS32387 to A.L.G.), the Lucille P. Markey Charitable Trust, Medical Research Council of Canada (MT-12554 to M.C.), and the Heart and Stroke Foundation of Canada (M.C.). A.L.G. is an Established Investigator of the American Heart Association, and M.C. is a Research Scholar of the Heart and Stroke Foundation of Canada.
Keywords
- Ion channel
- Myotonic dystrophy
- Phosphorylation
- Skeletal muscle
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Biophysics
- Structural Biology
- Biochemistry
- Cell Biology
