The Journal of Neurophysiology Vol. 84 No. 3 September 2000, pp. 1240-1246
Copyright ©2000 by the American Physiological Society

Novel Mechanism for Presynaptic Inhibition: GABA_A Receptors Affect the Release Machinery

The Otto Loewi Minerva Center for Cellular and Molecular Neurobiology, Department of Neurobiology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

Parnas, I., G. Rashkovan, R. Ravin, and Y. Fischer. Novel Mechanism for Presynaptic Inhibition: GABA_A Receptors Affect the Release Machinery. J. Neurophysiol. 84: 1240-1246, 2000. Presynaptic inhibition is produced by increasing Cl conductance, resulting in an action potential of a smaller amplitude at the excitatory axon terminals. This, in turn, reduces Ca²⁺ entry to produce a smaller release. For this mechanism to operate, the "inhibitory" effect of shunting should last during the arrival of the "excitatory" action potential to its terminals, and to achieve that, the inhibitory action potential should precede the excitatory action potential. Using the crayfish neuromuscular preparation which is innervated by one excitatory axon and one inhibitory axon, we found, at 12°C, prominent presynaptic inhibition when the inhibitory action potential followed the excitatory action potential by 1, and even 2, ms. The presynaptic excitatory action potential and the excitatory nerve terminal current (ENTC) were not altered, and Ca²⁺ imaging at single release boutons showed that this "late" presynaptic inhibition did not result from a reduction in Ca²⁺ entry. Since 50 µM picrotoxin blocked this late component of presynaptic inhibition, we suggest that -aminobutyric acid-A (GABA_A) receptors reduce transmitter release also by a mechanism other than affecting Ca²⁺ entry.