A study has been made of the effects of Sr2+ and Ba2+ ions at synapses in isolated superior cervical ganglia of guinea-pigs. Intracellular recordings of membrane potential were made from ganglion cells in the presence of different concentrations of Ca2+, Sr2+ and Ba2+ ions. 2. The addition of Sr2+ (2-5 mM) caused little change in resting membrane potential; in contrast, Ba2+ (1-6 mM) always depolarized the cells and prolonged the duration of action potentials. 3. The resting frequency of spontaneous miniature excitatory post-synaptic potentials (min. e.p.s.p.s) was briefly accelerated by the addition of either Sr2+ or Ba2+, but subsequently returned to about control levels. 4. Following replacement of Ca2+ by Sr2+, e.p.s.p.s could always be evoked during repetitive stimulation of preganglionic axons at a fixed latency after the nerve impulses ('phasic' transmitter release). Replacement of Ca2+ by Ba2+ produced many asynchronous e.p.s.p.s during trains of impulses ('residual' transmitter release). 5. By analysis of the interaction between Sr2+ and Ca2+, Sr2+ was shown to have a partial agonist action on 'phasic' transmitter release. The same analysis applied to Ba2+ failed to demonstrate either a partial agonist or antagonist action. 6. Both Sr2+ and Ba2+ prolonged e.p.s.p.s. Changes in Sr2+ could mainly be attributed to its effect on cell input resistance; Ba2+ may also prolong the time course of transmitter release. 7. The increased frequency of min. e.p.s.p.s which occurs during repetitive stimulation was potentiated by both Sr2+ and Ba2+, Ba2+ being about twice as potent as Sr2+. This activation of 'residual' transmitter release is independent of the action of these ions on 'phasic' release. 8. It is concluded that the reported maintenance by Ba2+ of acetyl-choline output from perfused ganglia results from the asynchronous release of large numbers of quanta during trains of impulses.
