Calcium-dependent, slow desensitization distinguishes different types of glutamate receptors.
1. L-Glutamate, the most likely transmitter of rapid excitatory synaptic interactions in the brain and spinal cord, is a potent neurotoxin. Mechanisms that terminate the action of glutamate are, therefore, likely to be important for maintaining the integrity of glutaminoceptive neurons. In this study, we show that glutamate currents evoked in voltage-clamped chick motoneurons fade during prolonged or repeated application of glutamate by pressure ejection from nearby pipettes. 2. The magnitude of the decline depends on the Ca2+/Mg2+ ratio in the extracellular medium. With Ca2+ = 10.0 mM and no added Mg, the steady-state glutamate current amounted to 50% of the initial value. 3. Single-channel measurements indicate that the fade is due to receptor desensitization rather than to agonist-induced channel blockade, as the mean channel open time within bursts is independent of the agonist concentration. 4. Application of more selective agonists showed that Ca2+-dependent slow desensitization involved only G1 (NMDA) receptors. G2 responses (activated by kainate and quisqualate) did not exhibit this slow phase of desensitization under the same conditions.
Zorumski
C F
CF
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.
Yang
J
J
Fischbach
G D
GD
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002645:Chickens; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000596:Amino Acids; D002413:Cations, Divalent; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate