Activation of a heart chloride current during stimulation of protein kinase C.
The whole-cell arrangement of the patch-clamp technique was used to examine the effect of protein kinase C (PKC) stimulation on ion channels in isolated guinea pig ventricular cells. In the presence of appropriate external solutions and drugs to reduce contamination from sodium, calcium, and potassium ion currents, application of phorbol 12-myristate 13-acetate or phorbol 12,13-dibutyrate, to stimulate PKC, activated a time-independent background current. The current-voltage relation for the PKC-activated current was linear over the voltage range of -90 to +60 mV. Alteration of the chloride equilibrium potential, brought about through changes in external and internal Cl- concentrations, shifted the reversal potential for the background current in a manner expected for a Cl- -selective ion channel. The PKC-activated current was reversibly inhibited by the S-(-)-enantiomer of the monocarboxylic acid derivative 8-chlorophenoxyproprionic acid, at a concentration that did not affect Ca2+ or delayed rectifier K+ currents. Dialysis of ventricular cells with partially purified PKC obtained from rat brain resulted in the activation of a large (greater than 1-nA) time-independent background current after addition of external phorbol 12,13-dibutyrate. In the presence of the beta-adrenergic receptor antagonist propranolol, norepinephrine activated a background current with properties similar to those of the PKC-sensitive current. It is concluded that cardiac ventricular cells contain PKC-activated Cl- channels, which may be regulated during alpha-adrenergic stimulation.
Walsh
K B
KB
Department of Pharmacology, University of South Carolina, School of Medicine, Columbia 29208.
D000818:Animals; D018118:Chloride Channels; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018118:Chloride Channels; D008565:Membrane Proteins; D015240:Phorbol 12,13-Dibutyrate; D011433:Propranolol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine