Potent inhibition by trivalent cations of ATP-gated channels

The effects of La3+ and other trivalent cations on ATP-gated channels (P2X purinoceptor/channels) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing these channels. La3+, Gd3+, Ce3+ and Nd3+ (30-300 microM) inhibited an inward current activated by 30 microM ATP in PC12 cells. The concentration-response curve for the ATP-activated current was shifted by La3+ or Gd3+ toward a higher concentration range, and the slope of the curve became steeper, suggesting the inhibition is non-competitive. La3+ or Gd3+ did not affect the current component that was slowly activated upon hyperpolarization, and selectively inhibited the remaining 'voltage-independent' component. La3+ and Gd3+ also inhibited currents mediated through P2X1 and P2X2 purinoceptors expressed in Xenopus oocytes. The results suggest that La3+ and other trivalent cations inhibit P2X purinoceptors at low concentrations. The inhibition may at least partly be attributed to an allosteric inhibition.