A SIMULATION OF ACTION-POTENTIALS IN SYNAPTIC BOUTONS DURING PRESYNAPTIC INHIBITION

1. During presynaptic inhibition, an increased conductance in the memb rane of the presynaptic bouton is presumed to reduce the action potent ial, thereby reducing transmitter release. The object of the simulatio n has been to determine the magnitude of a chloride conductance requir ed to reduce transmitter release, for various diameters of synaptic bo utons, connected to axons with diameters in the range 0.1-1.0 mu m. 2. A propagating action potential was simulated in axons connected to ei ther side of a hemispherical bouton. The axons could be myelinated or unmyelinated, while the bouton membrane could be passive, a node of th e myelinated nerve, or have the same active properties as the attached unmyelinated nerve. Membrane properties of the axons were derived fro m mammalian data and scaled to 37 degrees C. 3. A steady-state chlorid e conductance was included in the bouton membrane, with E(cl) = -40 mV . The amplitude of the action potential in the bouton was calculated f or different diameters of axon and bouton and for different magnitudes of chloride conductance. 4. Using published data on the relationship between the amplitude of a presynaptic action potential and the result ing postsynaptic potential, the relationship between the chloride cond uctance and the postsynaptic response was calculated for different geo metries. Transmitter release was reduced when an action potential was 90 mV or smaller, with no transmission for action potentials smaller t han 50 mV. 5. Conductance increases in the range 3 to 10 nS were requi red to reduce the action potential to 90 mV, depending on the diameter of the axon (0.5-1.0 mu m), diameter of the bouton (3-6 mu m), whethe r the bouton had passive or active membrane, and whether the axon was myelinated or unmyelinated. A 3 mu m passive bouton connected to a 0.5 mu m myelinated axon was most sensitive to the effects of a chloride conductance, while a 6 mu m active bouton connected to a 1 mu m myelin ated nerve was least sensitive to the effects of a chloride conductanc e. 6. The reduction in the action potential was compared when E(cl) = -40 mV and when E(cl) = E(rest) = -80 mV. inactivation of the sodium c onductance by terminal depolarization was the dominant influence on th e amplitude of the action potential. 7. Conductances that were suffici ent to completely block synaptic transmission at a bouton were insuffi cient to prevent the spread of the action potential away from that bou ton. 8. Schemes involving three boutons en passant, or three boutons t erminating an axon, with the boutons linked by small diameter(0.l-1.0 mu m) axons of length 10 mu m, required conductances in the range 200 pS-3 nS on all three boutons to reduce the action potential to 90 mV. 9. These calculations are integrated with the quantal conductance for gamma-aminobutyric acid (GABA), and the convergence of axoaxonic conta cts onto presynaptic terminals to determine whetherthe conductance inc reases required for presynaptic inhibition are likely to occur. It is suggested that it will be difficult to achieve a sufficiently large ch loride conductance to make a significant reduction in transmitter rele ase. However, the depolarization associated with the chloride conducta nce may have a direct inactivating action on high threshold calcium ch annels in the terminal membrane, thereby contributing to presynaptic i nhibition.