Inhibitory modulation of fast and slow Ca 2+-currents in neuroblastoma × glioma cells during differentiation

Abstract

Mouse neuroblastoma × rat glioma hybrid cells (N × G, 108CC15) were used to study the inhibitory effects of the synthetic opioid d-Ala 2- d-Leu 5-enkephalin (DADLE), somatostatin, adrenaline- α 2 and angiotensin II on voltage-dependent Ca 2+-currents (I Ca) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N × G cells with pertussis toxin or intracellular infusion of GDP βS 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 ω-conotoxin GVIA (ω-CTX) and methoxyverapamil (D600) as specific Ca 2+-channel blockers of the N- and L-type Ca 2+-channels, it was found that in N × G cells DADLE predominantly induces inhibition of T- and N-type Ca 2+-channels.