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Modulation of rat skeletal muscle chloride channels by activators and inhibitors of protein kinase C

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Abstract

The membrane electrical parameters and component conductances of rat extensor digitorum longus muscle fibres were studied in vitro at 30 °C with standard two microelectrode square pulse cable analysis in the presence of protein kinase C (PKC) activators and inhibitors. The PKC activator, 4-β-phorbol-12,13 dibutyrate (4-β-PDB), (2–90nM) blocked up to 67% chloride conductance (G Cl) in rat skeletal muscle fibres and induced myotonic hyperexcitability. The concentration necessary to produce a 50% block of the membrane G Cl was 23 nM. The “inactive” 4-α-phorbol-12,13 dibutyrate had no effect at 2 μM. The blocking effect of 4-β-PDB on G Cl was prevented by preincubation of the preparations with the PKC inhibitors, staurosporine (1–5 μM) and tetrahydropapaverolone (50–100 μM). The blocking effects on membrane G Cl of 4-β-PDB and its antagonism by the inhibitors used support the concept of the involvement of PKC in regulating Cl channels of mammalian skeletal muscle fibres.

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Tricarico, D., Conte Camerino, D., Govoni, S. et al. Modulation of rat skeletal muscle chloride channels by activators and inhibitors of protein kinase C. Pflugers Arch. 418, 500–503 (1991). https://doi.org/10.1007/BF00497778

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  • DOI: https://doi.org/10.1007/BF00497778

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