Stimulation of beta‐adrenoceptors inhibits calcium‐dependent potassium‐channels in mouse macrophages

K + efflux in mouse macrophages exhibited a rate constant (k K ) of 0.67 ± 0.04 (h) −1 (mean ± SEM of 16 experiments). This was strongly stimulated by increasing concentrations of the Ca 2+ ionophore A23187 up to a maximal value of 4.01 ± 0.25 (h) −1 with an IC 50 of 7.6 ± 1.9 μM (mean ± SEM of 6 experiments). Similar results were obtained with the Ca 2+ ionophore ionomycin. Binding experiments with 3 H‐dihydroalprenolol revealed a high density of beta‐adrenergic receptors (97.5 ± 5.2 fmol/mg protein) with apparent dissociation constant of 2.03 ± 0.06 nM. Isoproterenol at a concentration of 10 −6 ‐10 −5 M induced a two‐ to threefold stimulation of endogenous levels of cyclic AMP (cAMP). A23187‐stimulated K + efflux was partially inhibited by (i) stimulation of adenylate cyclase with isoproterenol, forskolin or, PG 1 ; (ii) exogenous cAMP; and (iii) inhibition of phosphodiesterase with MIX (1‐methyl‐3‐isobutylxanthine). Maximal inhibition of K + efflux was obtained by simultaneous addition of isoproterenol and MIX. In dose‐response curves, the isoproterenol‐sensitive K + efflux was half‐maximally inhibited (IC 50 ) with 2–5 × 10 −10 M of isoproterenol concentration. Propranolol was able to completely block the effect of isoproterenol, with an IC 50 of about 1–2 × 10 −7 M. Isoproterenol and MIX were also able to partially inhibit ionomycin‐stimulated K + efflux. Isoproterenol and MIX did not inhibit A23187‐stimulated K + efflux in an incubation medium where NaCI was replaced by sucrose (or choline), suggesting the involvement of an Na + : Ca 2+ exchange mechanism. Our results show that stimulation of beta‐adrenoceptors in mouse macrophages counterbalances the opening of K + channels induced by the calcium ionophore A23187. This likely reflects a decrease in cytosolic free calcium content via a cAMP‐mediated stimulation of Na + :Ca 2+ exchange.