Inhibitory Effects of Metals on ATP-Induced Current Through P2X7 Receptor in NG108-15 Cells

Abstract

We investigated the effects of heavy metal ions on the ATP-induced nonselective cation current through P2X7 receptor (INS.P2X7) in NG 108-15 cells using the whole-cell patch-clamp technique. Cu2+ inhibited the INS.P2X7 most potently among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+ also inhibited the INS.P2X7 in concentration-dependent manners. The order of potency was Cu2+ ≫ Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79 μ M, 1.2 μ M, 3.0 μ M and 4.6 μ M, respectively. Fe3+ (10 and 100 μ M) and Mn2+ (10 μ M) did not affect the INP.2X7. A high concentration of Mn2+ (100 μ M) slightly inhibited the INS.P2X7. When the concentration-response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the maximal response but not the EC50 value appeared to be reduced, suggesting that the inhibition is not competitive. These results suggest that under physiological and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and Co2+, may modulate P2X7 receptor channels as inhibitors.