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.
Desensitization of AMPA receptors limits the amplitude of EPSPs and the excitabitily of motoneurons of the rat isolated spinal cord / Ballerini, L.; Bracci, E.; Nistri, A.. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 7:6(1995), pp. 1229-1234. [10.1111/j.1460-9568.1995.tb01113.x]
Desensitization of AMPA receptors limits the amplitude of EPSPs and the excitabitily of motoneurons of the rat isolated spinal cord
Ballerini, L.;Nistri, A.
1995-01-01
Abstract
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.File | Dimensione | Formato | |
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