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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, 2001; 8(18):1372-1379
Publisher: Nature Publishing Group
Issue Date: 2001
ISSN: 0969-7128
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 2030 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 3032 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
RMID: 0020081577
DOI: 10.1038/
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Appears in Collections:Molecular and Biomedical Science publications

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