1. The inhibitory effects of lanthanide cations (Ln3+) on mechanical responses and 45Ca uptake in guinea‐pig ileal longitudinal smooth muscle were studied. 2. Ln3+ strongly inhibited the phasic and tonic component of the response to the muscarinic agonist cis‐2‐methyl‐4‐dimethylaminomethyl‐1,3‐dioxolane methiodide (CD) the two components being affected to the same extent. Inhibition was also obtained for the responses evoked by high K+ but here the effect was mainly on the phasic response, the tonic component was merely delayed. 3. Other members of the Ln3+ series, with the exception of cerium, were found to be more effective than lanthanum in their ability to inhibit the CD response. Thulium, Tm3+, the thirteenth member of the series was the most effective cation. 4. Analysis of 170Tm uptake revealed at least two components. The concentration‐dependence of one component, saturating at 2‐5 x 10(‐6) Tm, corresponded closely to that of the inhibitory effect of Tm3+ on contraction. 5. 170Tm uptake as a function of time showed a secondary rise after 30 min of exposure to the lanthanide. 6. Although 2‐5 x 10(‐6) M‐Tm3+ produced 90% inhibition of the CD and the high K+ induced responses significant reduction of 45Ca uptake by the muscle was only detected when much higher Tm3+ concentrations (greater than or equal 10(‐3) M‐Tm3+) were used. 7. It is concluded that Ln3+ combine with membrane sites specifically involved in Ca2+ translocation during excitation‐contraction coupling.
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