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https://hdl.handle.net/2440/47276
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Type: | Journal article |
Title: | Viral vector-mediated expression of K+ channels regulates electrical excitability in skeletal muscle |
Author: | Falk, T. Kilani, R. Yool, A. Sherman, S. |
Citation: | Gene Therapy (Basingstoke), 2001; 8(18):1372-1379 |
Publisher: | Nature Publishing Group |
Issue Date: | 2001 |
ISSN: | 0969-7128 1476-5462 |
Abstract: | Modification of K+ 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⁺ currents, we expressed a modified voltage-dependent K⁺ 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 studied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K⁺ conductance by 2030 h after infection. This increase in K⁺ 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⁺ channel toxin anemone toxin II (1 μM) was effectively counteracted by overexpression of Kv1.4 at 3032 h after transduction. Thus, virally induced overexpression of a voltage-gated K⁺ channel in skeletal muscle has a powerful effect in reducing electrical excitability. |
Keywords: | hyperkalemic periodic paralysis anemone toxin II herpes simplex 1 amplicon system green fluorescent protein Kv1.4 primary muscle culture |
DOI: | 10.1038/sj.gt.3301539 |
Published version: | http://www.nature.com/gt/journal/v8/n18/abs/3301539a.html |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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