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Eur J Neurosci. 1995 Jun 1;7(6):1229-34.

Desensitization of AMPA receptors limits the amplitude of EPSPs and the excitability of motoneurons of the rat isolated spinal cord.

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Biophysics Sector, International School for Advanced Studies (S.I.S.S.A), Trieste, Italy.


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.

[Indexed for MEDLINE]

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