Both d- and l-glutamate induce transporter-mediated presynaptic autoinhibition of transmitter release.
In crayfish motor nerve terminals l-glutamate (Glu) is the excitatory transmitter and low l-Glu concentrations exert autoinhibition by inhibiting release of Glu quanta from the terminals. This autoinhibition has been shown to be mediated by binding and transport of l-Glu by Glu transporters in the presynaptic membrane. Activated transporters open an associated Cl(-) channel and inhibit release [J. Dudel & M. Schramm (2003) Eur. J. Neurosci., 18, 902-910]. The excitatory, glutamatergic synaptic transmission is specific for the l-Glu isomer. However, transporters are non-selective for the stereoisomers. It is shown here that low concentrations (5 micro m) of d- as well as l-Glu inhibit quantal release on average to 55 and 68%, respectively. The power of inhibition varies widely at different terminals but the local sensitivity to d-Glu is seen to be the same as that for l-Glu. l-Glutamate has been reported to reduce the mean amplitude of nerve terminal action currents (excitatory nerve terminal currents) by about 10%, presumably due to the opening of Cl(-) channels. Evidence is given that d-Glu also inhibits this by an average of 10% (P < 0.001), as expected if both l- and d-Glu activate a transporter-associated Cl(-) conductance. The results give further support for this novel mechanism of regulation of synaptic strength.
Dudel
Josef
J
Physiologisches Institut der Ludwig-Maximilians-Universität München, Schillerstrasse 46, D-80336 München, Germany. dudel@lrz.uni-muenchen.de
D000818:Animals; D003400:Astacoidea; D004594:Electrophysiology / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D026901:Membrane Transport Proteins / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals; D009435:Synaptic Transmission / Q000187:drug effects
D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; D018698:Glutamic Acid