Pflügers Archiv

, Volume 418, Issue 5, pp 500–503 | Cite as

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

  • D. Tricarico
  • D. Conte Camerino
  • S. Govoni
  • S. H. Bryant
Excitable Tissues and Central Nervous Physiology

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 (GCl) in rat skeletal muscle fibres and induced myotonic hyperexcitability. The concentration necessary to produce a 50% block of the membrane GCl 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 GCl 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 GCl 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.

Key words

Rat skeletal muscle Phorbol esters Staurosporine Protein kinase C Chloride channels 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • D. Tricarico
    • 1
  • D. Conte Camerino
    • 1
  • S. Govoni
    • 1
  • S. H. Bryant
    • 2
  1. 1.Unità di Farmacologia, Dipartimento FarmacobiologicoFacoltà di FarmaciaBariItaly
  2. 2.Department of Pharmacology and Cell BiophysicsUniversity of CincinnatiOhioUSA

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