Desensitization of AMPA receptors limits the amplitude of EPSPs and the excitability of motoneurons of the rat isolated spinal cord.
Intracellular recording was used to study the effect of cyclothiazide, a selective blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on lumbar motoneurons of the rat isolated spinal cord. Cyclothiazide (25 microM) enhanced the responses to AMPA in a tetrodotoxin-insensitive fashion, without affecting those produced by N-methyl-D-aspartate or gamma-aminobutyric acid. Excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation were strongly potentiated in amplitude while paired-pulse depression (produced by applying pairs of pulses at 2 s interval) of the EPSP was decreased. In the presence of cyclothiazide the frequency of spontaneous synaptic events was greatly increased and network-driven bursting activity developed with eventual loss of electrical excitability. The present results suggest that pharmacological block of AMPA receptor desensitization led to strong excitation of motoneurons and indicate a physiological role of desensitization in protecting these nerve cells from overactivity.
Ballerini
L
L
Biophysics Sector, International School for Advanced Studies (S.I.S.S.A), Trieste, Italy.
Bracci
E
E
Nistri
A
A
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001581:Benzothiadiazines; D018091:Receptors, AMPA; D013779:Tetrodotoxin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide