Effect of treatment time on calcium antagonism by cadmium ions in a guinea-pig taenia coli.

1. When pretreated for 1 min, with Cd2+ at low concentrations (0.001-0.01 mM), there was a parallel rightward shift of Ca2+ concentration-curves in guinea-pig taenia coli in K+-depolarized Ca2+-free medium. However, when pretreated for 30 min, Cd2+ reduced the maximal Ca2+ response size. 2. The application of 0.01 mM Cd2+ for 1, 5 and 30 min in Ca2+-free, K+-medium reduced to the same degree the Ca uptake after addition of 3 mM Ca2+. The inhibitory action on the tension by Cd2+ however, became greater as the pretreatment time with Cd2+ increased. 3. Within 5 min of Cd2+ (0.01 mM) treatment, Cd2+ chiefly bound to the cell membrane, however, with a longer duration (30 min), Cd2+ entered the cytoplasm where EDTA could not reach. 4. Cd2+ above 0.0005 mM reduced dose-dependently the respiration of isolated mitochondria. 5. These results suggest that with short duration exposure (1-5 min) of taenia coli cells to Cd2+, the interference with Ca2+ entry through voltage-dependent Ca2+ channels is predominant but for longer exposure times, intracellular actions of Cd2+ contribute to its inhibitory effects.