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 (I_ns) were investigated using smooth-muscle cells of the rabbit portal vein. Neither bath application of the PKC activator, phorbol 12,13-dibutyrate (PDBu; 1 μM), nor the internal application of guanosine 5′-[γ-thio]-triphosphate (GTP[γS]; 3 μM) elicited any current at the holding potential of -60 mV. However, when GTP[γS] (3 μM) 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, 4α-phorbol 12,13-didecanoate (300 nM and 1 μM) had no effect on the membrane current even when GTP[γS] (3 μM) was in the pipette. The current amplitude induced by PDBu in the presence of GTP[γS] in the pipette was markedly reduced following pretreatment with 10 μM 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 I_ns. An internal application of pertussis toxin markedly reduced the amplitude of I_ns induced by PDBu. These results indicate that PKC activates a sustained component of I_ns in cooperation with an activated pertussis-toxin-sensitive G protein in the rabbit portal vein.