Barium and strontium can substitute for calcium in noradrenaline output induced by excess potassium in the guinea-pig.

1. The ability of Ba2+ and Sr2+ to substitute for Ca2+ in the noradrenaline output induced by excess K+ was examined using isolated guinea-pig vas deferens. 2. When the vas deferens was repeatedly exposed to excess K+ (60 mM) at 40 min intervals, the noradrenaline output increased at least three-fold in incubation medium which contained either Ca2+, Ba2+ or Sr2+. The response decreased on repetition. The order of effectiveness was roughly Ba2+ > Ca2+ > Sr2+. 3. In the absence of excess K+, these cations had no significant stimulating effect on the noradrenaline output even when added after exposure to Ca2+-free solution. 4. As the concentration of divalent cation was increased from 0.2 to 2.5 mM the noradrenaline output induced by excess K+ increased. The maximum noradrenaline output was achieved at a divalent cation concentration of 2.5 mM and was 29.56 +/- 3.52, 15.02 +/- 1.12 and 7.45 +/- 0.84 (mean +/- S.E. of mean) n-mole/g per hr in the presence of either Ba2+, Ca2+ or Sr2+, respectively. Further increase in the concentration of the cations reduced the response. 5. The addition of either Sr2+ (2 mM) or Ca2+ (1 mM) to a solution containing various concentrations of Ba2+ facilitated the K+-induced increase in the noradrenaline output when the Ba2+ concentration was low, but inhibited release of noradrenaline when higher concentrations of Ba2+ were used. The addition of Sr2+ (1 mM) to Ca2+-containing solutions had a similar effect. 6. Mg2+ competitively inhibited the K+-induced increase in the noradrenaline output in the presence of either Ba2+ or Sr2+ and blocked that in the presence of CA2+. 7. The results indicate that both Ba2+ and Sr2+ can substitute for Ca2+ in the cations act though the same site at some stage in the process of K+-induced transmitter release.