title: Modulation of rat skeletal muscle chloride channels by activators and inhibitors of protein kinase C.
abstract: 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.
authors.affiliation: Unità di Farmacologia, Dipartimento Farmacobiologico, Facoltà di Farmacia, Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Tricarico
authors.forename: D
authors.initials: D
authors.lastname: Conte Camerino
authors.forename: S
authors.initials: S
authors.lastname: Govoni
authors.forename: S H
authors.initials: SH
authors.lastname: Bryant
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013765:Tetrahydropapaveroline / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D018118:Chloride Channels; D002712:Chlorides; D007546:Isoquinolines; D008565:Membrane Proteins; D010879:Piperazines; D015240:Phorbol 12,13-Dibutyrate; D013765:Tetrahydropapaveroline; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine