REGULATION OF RESTING IONIC CONDUCTANCES IN FROG SKELETAL-MUSCLE

The membrane electrical properties and resting ionic conductances of frog semitendinosus muscle fibres were studied in vitro at 25-degrees-C with the two-microelectrode cable technique, in the presence of an activator or inhibitor of protein kinase C (PKC) or in the presence of an activator of adenylate cyclase. The PKC activator, 4beta-phorbol 12,13-dibutyrate (4beta-PDB), reduced chloride conductance (G(Cl)) at concentrations greater than 1 muM and did not affect potassium conductance (G(K)). At 150 muM, the maximum concentration of 4beta-PDB tested, G(Cl) was reduced by 42%. The ''inactive'' phorbol ester 4alpha-phorbol 12,13-dibutyrate did not affect G(Cl) or G(K). The inhibitory effect of 4beta-PDB on G(Cl) was prevented by pretreatment of the muscle preparation with the PKC inhibitor staurosporine. The adenylate cyclase activator forskolin (1.5-8 muM) significantly increased the G(K) Of the fibres, without affecting G(Cl). Thus, we conclude that frog skeletal muscle G(Cl), unlike rat muscle G(Cl), is relatively insensitive to activators of PKC. Moreover, in frog muscle, protein kinase A is a likely modulator of G(K), but not G(Cl).