Combined actions of Pb2+, Zn2+, and Al3+ on voltage-activated calcium channel currents

1. Whole-cell patch clamp experiments were performed on rat dorsal root ganglion (DRG) neurons to investigate the actions of various combinations of Pb2+, Zn2+, and Al3+ on voltage-activated calcium channel currents (VACCCs). 2. Each of these metals has been shown to reduce VACCCs. 3. We investigated the effects of simultaneous application of two cations in the range of their IC50 values. For all possible combinations (Pb2+/Zn2+, Zn2+/Al3+, Al3+/Pb2+), independent of the order of application, we found additive actions on VACCCs. 4. We observed a 75% (+/- 9%) block of the control current when two cations were applied simultaneously. This observation is consistent with both, an action of two metals at the same site as well as independent actions at different locations of the ion channel. 5. The additivity of the effects should be taken into account for questions of public health and the assessment of threshold limits in cases of environmental contamination.