Electrophysiologic and biochemical studies on the putative Ca⁺⁺ channel blocker MDL 12,330A in an endocrine cell

MDL 12,330A is a molecule structurally unrelated to other organic Ca⁺⁺ channel ligands that may alter Ca⁺⁺ channel function. Using whole cell patch clamp, [³h]PN200-110 binding and ⁴⁵Ca⁺⁺ uptake studies, we examined the effects of this compound on voltage-dependent Ca⁺⁺ channels in rat anterior pituitary cells. At a concentration of 10^-5 M, MDL 12,330A showed little effect on outward K⁺ current, Na⁺ current or low-threshold Ca⁺⁺ current in this cell line. At 10^-6 M, MDL 12,330A reversibly inhibited slow Ca⁺⁺ current in a voltage-dependent manner. ⁴⁵Ca⁺⁺ uptake was also blocked by this compound at 10^-6 M, whereas [³H]PN200-110 binding was stimulated at concentrations of 10^-7 to 10^-6 M. The results are consistent with an interaction of MDL 12,330A with slow Ca⁺⁺ channels at a site allosterically linked to the 1,4-dihydropyridine binding site.