Facilitation of Ca2+ action potential frequency by a small G protein Rab3A in rat pituitary GH3 cells.

GH3 pituitary cells have high tendency to exhibit spontaneous Ca2+ action potentials and their frequency (Ca2+ APF) is increased by treatment with thyrotropin-releasing hormone (TRH). Although spontaneous Ca2+ firing was thought to be significant for the induction of oscillations in cytosolic Ca2+ concentration ([Ca2+]i), little attempt to elucidate the mechanism has been done so far. We demonstrate here that spontaneous Ca2+ APF in GH3 cells was increased 1.5-3 fold, comparable to that for TRH, by injection of guanosine 5'-0-3-thiotriphosphate (GTPgammaS), rab3A effector domain peptide, and phorbol-dibutyrate (PDBu), whereas guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), H-rab5 peptide, ras peptide, and 4 alpha-phorbol did not. The enhancement of Ca2+ firing by rab3A effector domain peptide was blocked by a protein kinase C (PKC) inhibitor, PKC(19-36). The present study suggests that the spontaneous Ca2+APF may be controlled by small G protein phosphorylated by PKC.