EFFECTS OF INORGANIC MERCURY (HG2+) ON CALCIUM-CHANNEL CURRENTS AND CATECHOLAMINE RELEASE FROM BOVINE CHROMAFFIN CELLS

The effects of inorganic mercury (Hg2+) on calcium channel currents and the potassium-evoked catecholamine release of bovine chromaffin cells in culture were examined. The effects of cadmium (Cd2+), known to block calcium channels and reduce catecholamine release of chromaffin cells, were studied for comparison. Calcium channel currents were recorded in the whole-cell configuration of the patch-clamp technique. Hg2+ is a potent calcium channel blocker in bovine chromaffin cells. The IC50 value is about 3 mu M, the Hill slope 1.46. In a concentration of 100 mu M, Hg2+ blocked the currents completely; 100 mu M Cd2+ had the same effect. Potassium-evoked catecholamine release from chromaffin cells was measured at different time-points with high-performance-liquid-chromatography (HPLC) under control conditions and in the presence of different Hg2+ concentrations. Low Hg2+ concentrations (0.1 and 1 mu M) did not affect the amount of the catecholamines epinephrine (E) and norepinephrine (NE) which was released. Under identical conditions 1 mu M Cd2+ also had no effect on release. With 10 mu M Hg2+ there was a time-dependent increase in the potassium-evoked catecholamine release (by 27% after 8 min). The E/NE ratio was not altered, suggesting that the release of both hormones was increased similarly. In contrast to this, the release was slightly reduced with 10 mu M Cd2+. In the presence of 100 mu M Hg2+, there was a reduction of the release during an early phase, followed by an increase. The reduction is most probably due to the fast and effective calcium channel block by Hg2+ in this high concentration. The calcium channel block by 100 mu M Cd2+ also reduced the release significantly. Catecholamine release of bovine chromaffin cells is driven into two opposite directions by Hg2+. On the one hand, a calcium channel block reduces the release, while on the other hand effects occur which can increase the release. Both tendencies occur simultaneously, but have different concentration- and time-dependencies; therefore one can overcome the other under specific conditions. The catecholamine output at a given timepoint reflects the ''sum'' of these different effects.