| Autor: |
Falk, T, Kilani, R K, Yool, A J, Sherman, S J |
| Předmět: |
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| Zdroj: |
Gene Therapy; Sep2001, Vol. 8 Issue 18, p1372, 8p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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