The gadolinium ion: a potent blocker of calcium channels and catecholamine release from cultured chromaffin cells

Gadolinium (Gd³⁺) is a trivalent ion of the lanthanide series which has a high charge density and a similar ionic radius to Ca²⁺. The effects of gadolinium ions on ³H]noradrenaline output and ⁴⁵Ca fluxes during resting conditions and stimulation were investigated in cultured bovine chromaffin cells. Chromaffin cells isolated from bovine adrenal medullae were plated on collagen-coated dishes (10⁶ cells/dish) in a medium containing 10% fetal calf serum. Seven-day-old cells were used in all studies.Exposure of chromaffin cells to 0.05mM Gd³⁺ produced 80 ± 5% and 81 ± 4% inhibition of the secretory responses to 10^?4M acetylcholine and 56 mM K⁺ respectively. Doubling of the extracellular concentration of Gd³⁺ produced an 87 ± 3% and 100 ± 2% inhibition of the acetylcholine-induced and K⁺-induced release of ³H]noradrenaline. Gd³⁺ (0.05 mM) also produced a parallel shift to the right in the dose-response relationship between extracellular Ca²⁺ concentrations and ³H]noradrenaline output during acetylcholine stimulation. This observation suggests a competitive antagonism between Ca²⁺ and Gd³⁺ in stimulus-secretion coupling.Gd³⁺ (0.05 mM) was an effective inhibitor (92.3 ± 0.7%) of the uptake of ⁴⁵Ca into chromaffin cells induced by a depolarizing concentration (56 mM) of K⁺. Furthermore, Gd³⁺ also inhibited the increase in both Ca²⁺ ? Ca²⁺ exchange mechanism and ³H]noradrenaline output observed in chromaffin cells upon the reintroduction of Ca²⁺ into a Ca²⁺]-free incubation medium.The results, which were obtained using low concentrations of Gd³⁺, indicate that gadolinium is a powerful inhibitor of the Ca²⁺ movements which are required for triggering amine release from chromaffin cells by different secretagogues. Moreover, the results also suggest that Gd³⁺ might be a useful tool for release and electrophysiological studies in other Ca²⁺-dependent systems.