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- Title
Viral vector-mediated expression of K<sup>+</sup> channels regulates electrical excitability in skeletal muscle.
- Authors
Falk, T; Kilani, R K; Yool, A J; Sherman, S J
- Abstract
Modification of K[sup +] currents by exogenous gene expression may lead to therapeutic interventions in skeletal muscle diseases characterized by alterations in electrical excitability. In order to study the specific effects of increasing outward K[sup +] currents, we expressed a modified voltage-dependent K[sup +] channel in primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed as an N-terminal fusion protein containing a bioluminescent marker (green fluorescent protein). Transgene expression was carried out using the helper-dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using fluorescein optics and stud- ied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K[sup +] conductance by 20-30 h after infection. This increase in K[sup +] current led to a decrease in membrane resistance and a 10-fold increase in the current threshold for action potential generation. Electrical hyperexcitability induced by the Na[sup +] channel toxin anemone toxin II (1 µM) was effectively counteracted by overexpression of Kv1.4 at 30-32 h after transduction. Thus, virally induced overexpression of a voltage-gated K[sup +] channel in skeletal muscle has a powerful effect in reducing electrical excitability.
- Subjects
PARALYSIS; GENE expression; MUSCULOSKELETAL system; GREEN fluorescent protein
- Publication
Gene Therapy, 2001, Vol 8, Issue 18, p1372
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301539