Novel Mechanism for Presynaptic Inhibition: GABA_AReceptors Affect the Release Machinery

Abstract

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 Ca(2+) 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 degrees 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 Ca(2+) imaging at single release boutons showed that this "late" presynaptic inhibition did not result from a reduction in Ca(2+) entry. Since 50 microM 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 affecting Ca(2+) entry.

Glial Nitric Oxide-Mediated Long-Term Presynaptic Facilitation Revealed by Optical Imaging in Rat Spinal Dorsal Horn

“…The silent presynaptic afferent terminals may become activated after their liberation from the shunting of action potentials at the terminals (Cattaert and El Manira, 1999;MacDermott et al, 1999;Parnas et al, 2000;Cattaert et al, 2001;Lee et al, 2002) or from the conduction block of action potentials by inhibitory transmitters at the branching points (Wall, 1995). This study has exhibited that such liberation from the shunting of presynaptic spiking might also underlie LTP.…”

GABAergic synapses made by a retinal dopaminergic neuron

“…DA cells do contain GABA A receptors, uniformly distributed throughout their surface (30) as well as concentrated at the site of the synapses that DA cells receive from other GABAergic amacrines (23). Although examples exist in the literature of presynaptic inhibition mediated by presynaptic GABA A receptors (34,35), it seems unlikely that such receptors are concentrated at the release sites of the DA cell synapses. Finally, GABA A receptors are present in AII amacrine cells, because a Cl Ϫ conductance is activated in these neurons by muscimol, a GABA receptor agonist (36).…”

Effects of propofol and pentobarbital on calcium concentration in presynaptic boutons on a rat hippocampal neuron

“…Furthermore, it has been reported that GABA A receptors also reduce neurotransmitter release by another mechanism that does not affect Ca 2? entry [35]. Hence, at present, mechanisms of the inhibitory effects of propofol and pentobarbital on the changes in [Ca 2? ]…”

“…Moreover, Richards [18] demonstrated that many general anesthetics inhibited the action potential-evoked secretion of neurotransmitter in the CNS and that their inhibitory actions could be fully accounted for by their Propofol and pentobarbital modulate GABA A -receptormediated inhibition in postsynaptic events [1][2][3][4][5][6][7]. GABA A receptors are also located on presynaptic boutons [13,14,[32][33][34][35]. These receptors reduce Ca 2?…”