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

The membrane electrical parameters and component conductances of rat extensor digitorum longus muscle fibres were studied in vitro at 30 degrees C with standard two microelectrode square pulse cable analysis in the presence of protein kinase C (PKC) activators and inhibitors. The PKC activator, 4-beta-phorbol-12,13 dibutyrate (4-beta-PDB), (2-90 nM) 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-alpha-phorbol-12,13 dibutyrate had no effect at 2 microM. The blocking effect of 4-beta-PDB on GCl was prevented by preincubation of the preparations with the PKC inhibitors, staurosporine (1-5 microM) and tetrahydropapaverolone (50-100 microM). The blocking effects on membrane GCl of 4-beta-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.