Dual modulation of calcium channel current via recombinant [alpha]2-adrenoceptors in pheochromocytoma (PC-12) cells

The ability of recombinant rat α^sub 2D^-and α^sub 2B^-adrenoceptors expressed in nerve-growth-factor-differentiated pheochromocytoma PC-12 cells to modulate Ca^sup 2+^ currents, recorded by the whole-cell patch-clamp technique, has been studied. Ca^sup 2+^ currents in different cells were either reversibly reduced or increased by dexmedetomidine, an α^sub 2^-adrenergic agonist, in a concentration-dependent manner. Pertussis toxin pretreatment reduced the number of cells that showed an inhibitory response and reduced the magnitude of inhibition. In cells expressing the α^sub 2B^-adrenoceptor, pertussis toxin increased the proportion of cells from which a stimulatory effect on Ca^sup 2+^ currents could be recorded. The magnitude of the inhibitory responses was unaffected but the stimulatory responses were considerably reduced by the dihydropyridine Ca^sup 2+^ channel blocker nifedipine (5 μM). All effects of dexmedetomidine were reversible upon wash-out and inhibited by the antagonist rauwolscine. The results support the idea that modulation of voltage-dependent Ca^sup 2+^ channels in transfected PC-12 cells is mediated by activation of recombinant α^sub 2D^- and α^sub 2B^-adrenoceptors. This receptor activation predominantly causes inhibition of dihydropyridine-insensitive Ca^sup 2+^ channels via pertussis-toxin-sensitive G proteins. Additionally receptor activation can also lead to stimulation of dihydropyridine-sensitive Ca^sup 2+^ channels via pertussis-toxin-insensitive mechanisms.[PUBLICATION ABSTRACT]