Desensitization and resensitization rates of glutamate-activated channels may regulate motoneuron excitability.
1. Single-channel properties of desensitizing glutamate-activated channels were analyzed in outside-out patch-clamp recordings from a motoneuron-enriched cell fraction from embryonic chick. A piezo-driven device was used to achieve fast solution exchange at the electrode tip, resulting in maximum activation within 2 ms. 2. Quisqualate/AMPA receptors, with a 13-pS conductance, desensitized rapidly; the desensitization rate depended on agonist concentration but not on membrane potential. When quisqualate was applied slowly, the quisqualate-activated channels desensitized without prior channel opening, indicating desensitization from the closed state. After a 10-ms refractory period, resensitization of all channels required up to 300 ms; resensitization rate did not depend on the duration of the preceding quisqualate application. 3. At agonist concentrations less than or equal to 1 mM, kainate receptors, with a 20-pS conductance, did not desensitize. At kainate concentrations greater than or equal to 1 mM, though, kainate receptors desensitized to a low steady-state conductance within approximately 200 ms. Resensitization of all channels required as long as 3 s, which could render kainate receptors inexcitable during high-frequency activation. 4. Desensitization rates of whole-cell currents were similar to those observed in outside-out mode. Glutamate- and quisqualate-activated responses were similar, suggesting that the rapidly desensitizing quisqualate-sensitive receptor type may dominate the kinetics of whole-cell excitatory postsynaptic currents (EPSCs) in this preparation. 5. It may be concluded that the efficacy of glutamate-mediated synaptic transmission is modulated by differences in the rates of desensitization and resensitization.
Smith
D O
DO
Physiologisches Institut, Technischen Universität München, Germany.
Franke
C
C
Rosenheimer
J L
JL
Zufall
F
F
Hatt
H
H
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D009046:Motor Neurons / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D007473:Ion Channels; D011810:Quinoxalines; D007051:Ibotenic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid