Dual modulation of calcium channel current via recombinant α2-adrenoceptors in pheochromocytoma (PC-12) cells

 The ability of recombinant rat α_2D-and α_2B-adrenoceptors expressed in nerve-growth-factor-differentiated pheochromocytoma PC-12 cells to modulate Ca²⁺ currents, recorded by the whole-cell patch-clamp technique, has been studied. Ca²⁺ currents in different cells were either reversibly reduced or increased by dexmedetomidine, an α₂-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_2B-adrenoceptor, pertussis toxin increased the proportion of cells from which a stimulatory effect on Ca²⁺ currents could be recorded. The magnitude of the inhibitory responses was unaffected but the stimulatory responses were considerably reduced by the dihydropyridine Ca²⁺ 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 Ca²⁺ channels in transfected PC-12 cells is mediated by activation of recombinant α_2D- and α_2B-adrenoceptors. This receptor activation predominantly causes inhibition of dihydropyridine-insensitive Ca²⁺ channels via pertussis-toxin-sensitive G proteins. Additionally receptor activation can also lead to stimulation of dihydropyridine-sensitive Ca²⁺ channels via pertussis-toxin-insensitive mechanisms. Received: 25 March 1997 / Received after revision: 27 August 1997 / Accepted: 12 September 1997