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Differential Inhibition Of Sodium Currents By Divalent Cations In AtT-20/D16-16 Clonal Anterior Pituitary Cells

Voltage-gated sodium channels in the AtT20/D16-16 clonal anterior pituitary cell line were found to be exhibit a high sensitivity to block by divalent cations. Approximately 70% of the peak sodium conductance in patch-clamped cells was blocked by CO'+ or CdZ+ with IC50 values of 1.6 mM and 22 pM respectively. The reduction in sodium conductance appeared to be the result of a voltage-dependent channel block which was much more pronounced at negative voltages. About 30% of the sodium channels were relatively resistant to block with divalent cations, but all sodium channels were equally sensitive to tetrodotoxin with an apparent K, of 15 nM. By contrast, hybrid NG108-15 neuroblastoma xglioma cells showed only low affinity block with IC50 values of 41 mM for CO" or 16 mM for Cd2+. The divalent cation sensitive fraction of the AtT-20/D16-16 sodium channels were apparently responsible for failure to elicit sodium spikes in the presence of CdZ+ and CO''.