ACTION-POTENTIAL PROPAGATION AND PROPAGATION BLOCK BY GABA IN RAT POSTERIOR PITUITARY NERVE-TERMINALS

1. A theoretical model was developed to investigate action potential p ropagation in posterior pituitary nerve terminals. This model was then used to evaluate the efficacy of depolarizing and shunting GABA respo nses on action potential propagation. 2. Experimental data obtained fr om the posterior pituitary with patch clamp techniques were used to de rive empirical expressions for the voltage and time dependence of the nerve terminal Na+ and K+ channels. The essential structure employed h ere was based on anatomical and cable data from the posterior pituitar y, and consisted of a long cylindrical axon (diameter, 0.5 mm) with a large spherical swelling (diameter, 4-21 mm) in the middle. 3. In the absence of an inhibitory conductance, simulated action potentials prop agated with high fidelity through the nerve terminal. Swellings could block propagation, but only when sizes exceeded those observed in the posterior pituitary. Adding axonal branches reduced the critical size only slightly. These results suggested that action potentials invade t he entire posterior pituitary nerve terminal in the absence of inhibit ion or depression. 4. The addition of inhibitory conductance to a swel ling caused simulated action potentials to fail at the swelling. Depol arizing inhibitory conductances were 1.6 times more effective than shu nting inhibitory conductances in blocking propagation. 5. Inhibitory c onductances within the range of experimentally observed magnitudes and localized to swellings in the observed range of sizes were too weak t o block simulated action potentials. However, twofold enhancement of G ABA responses by neurosteroid resulted in currents strong enough to bl ock propagation in realistic swelling sizes. 6. GABA could block simul ated propagation without neurosteroid enhancement provided that GABA w as present throughout a region in the order of a few hundred micrometr es. For this widespread inhibition depolarizing conductance was 2.2 ti mes more effective than shunting conductance. 7. These results imply t wo modes of propagation block, one resulting from highly localized rel ease of inhibitory transmitter under conditions potentiating GABA resp onses, and the other resulting from widespread release of GABA in the absence of receptor potentiation. 8. The Na+ channels of the posterior pituitary nerve terminal have a unique voltage dependence that allows small depolarizations to inactivate without causing activation. The v oltage dependence of this Na+ channel may serve as a specialized adapt ation that facilitates in allowing small depolarizing conductances to block action potential propagation.