Novel mechanism for presynaptic inhibition: GABA(A) receptors affect the release machinery

Presynaptic inhibition is produced by increasing Cl- conductance, resulting in an action potential of a smaller amplitude at the excitatory axon termi nals. This, in turn, reduces Ca2+ entry to produce a smaller release. For t his mechanism to operate, the "inhibitory" effect of shunting should last d uring the arrival of the "excitatory" action potential to its terminals, an d to achieve that, the inhibitory action potential should precede the excit atory action potential. Using the crayfish neuromuscular preparation which is innervated by one excitatory axon and one inhibitory axon, we found, at 12 degrees C, prominent presynaptic inhibition when the inhibitory action p otential 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 reduc tion in Ca2+ entry. Since 50 mu M picrotoxin blocked this late component of presynaptic inhibition, we suggest that gamma- aminobutyric acid-A (GABA(A )) receptors reduce transmitter release also by a mechanism other than affe cting Ca2+ entry.