INHIBITORY MODULATION OF FAST AND SLOW CA2+-CURRENTS IN NEUROBLASTOMA X GLIOMA-CELLS DURING DIFFERENTIATION

Mouse neuroblastoma x rat glioma hybrid cells (N x G, 108CC15) were used to study the inhibitory effects of the synthetic opioid D-Ala2-D-Leu5-enkephalin (DADLE), somatostatin, adrenaline-alpha-2 and angiotensin II on voltage-dependent Ca2+ -currents (I(Ca)) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N x G cells with pertussis toxin or intracellular infusion of GDP-beta-S indicating an involvement of a pertussis toxin sensitive GTP-binding protein (G-protein), presumably G(o). The effect of DADLE, the strongest inhibitor of I(Ca), was studied during dibutyryl cyclic AMP (dBcAMP) induced differentiation. Using omega-conotoxin GVIA (omega-CTX) and methoxyverapamil (D600) as specific Ca2+ -channel blockers of the N- and L-type Ca2+ -channels, it was found that in N x G cells DADLE predominantly induces inhibition of T- and N-type Ca2+ -channels.