Protein kinase C activates the non-selective cation channel in the rabbit portal vein.

Effects of protein kinase C (PKC) on a non-selective cation channel current (Ins) were investigated using smooth-muscle cells of the rabbit portal vein. Neither bath application of the PKC activator, phorbol 12,13-dibutyrate (PDBu; 1 microM), nor the internal application of guanosine 5'-[gamma-thio]-triphosphate (GTP[gamma S]; 3 microM) elicited any current at the holding potential of -60 mV. However, when GTP[gamma S] (3 microM) was present in the pipette, PDBu elicited a sustained inward current, in a concentration-dependent manner, at the holding potential of -60 mV. On the other hand, an inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (300 nM and 1 microM) had no effect on the membrane current even when GTP[gamma S] (3 microM) was in the pipette. The current amplitude induced by PDBu in the presence of GTP[gamma S] in the pipette was markedly reduced following pretreatment with 10 microM staurosporine, a PKC inhibitor. Neither a reduction in the Cl- concentration in the pipette nor addition of niflumic acid to the bath inhibited the inward current, and the reversal potential estimated from the current/voltage relationship was about -5 mV (physiological salt solution containing 5 mM Ba2+/high CSCl), which revealed that the main component of the current is Ins. An internal application of pertussis toxin markedly reduced the amplitude of Ins induced by PDBu. These results indicate that PKC activates a sustained component of Ins in cooperation with an activated pertussis-toxin-sensitive G protein in the rabbit portal vein.