Viral vector-mediated expression of K+ channels regulates electrical excitability in skeletal muscle

T. Falk, R. K. Kilani, A. J. Yool, S. J. Sherman

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1372-1379
Number of pages8
JournalGene Therapy
Volume8
Issue number18
DOIs
StatePublished - Oct 6 2001

Keywords

  • Anemone toxin II
  • Green fluorescent protein
  • Herpes simplex 1 amplicon system
  • Hyperkalemic periodic paralysis
  • Kv1.4
  • Primary muscle culture

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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