Central cholinesterase inhibition enhances glutamatergic

Synaptic Transmission, Maxim Kozhemyakin, Karthik Rajasekaran, Jaideep Kapur

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration- dependent fashion. The amplitude of mEPSCs was not increased, which suggested the possibility of enhanced action potential-dependent release. Analysis of EPSCs evoked by minimal stimulation revealed reduced failures and increased amplitude of evoked responses. The ratio of amplitudes of EPSCs evoked by paired stimuli was also altered. The effect of paraoxon on glutamatergic transmission was blocked by the muscarinic antagonist atropine and partially mimicked by carbachol. The nicotinic receptor antagonist α -bungarotoxin did not block the effects of paraoxon; however, nicotine enhanced glutamatergic transmission. These studies suggested that cholinergic overstimulation enhances glutamatergic transmission by enhancing neurotransmitter release from presynaptic terminals.

Original languageEnglish (US)
Pages (from-to)1748-1757
Number of pages10
JournalJournal of Neurophysiology
Volume103
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Paraoxon
Cholinesterases
Cholinergic Agents
Seizures
Nicotinic Antagonists
Bungarotoxins
Muscarinic Antagonists
Organophosphates
Status Epilepticus
Excitatory Postsynaptic Potentials
Cholinesterase Inhibitors
Presynaptic Terminals
Nicotinic Receptors
Carbachol
Nicotine
Atropine
Synapses
Action Potentials
Neurotransmitter Agents

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Transmission, S., Kozhemyakin, M., Rajasekaran, K., & Kapur, J. (2010). Central cholinesterase inhibition enhances glutamatergic. Journal of Neurophysiology, 103(4), 1748-1757. https://doi.org/10.1152/jn.00949.2009

Central cholinesterase inhibition enhances glutamatergic. / Transmission, Synaptic; Kozhemyakin, Maxim; Rajasekaran, Karthik; Kapur, Jaideep.

In: Journal of Neurophysiology, Vol. 103, No. 4, 04.2010, p. 1748-1757.

Research output: Contribution to journalArticle

Transmission, S, Kozhemyakin, M, Rajasekaran, K & Kapur, J 2010, 'Central cholinesterase inhibition enhances glutamatergic', Journal of Neurophysiology, vol. 103, no. 4, pp. 1748-1757. https://doi.org/10.1152/jn.00949.2009
Transmission S, Kozhemyakin M, Rajasekaran K, Kapur J. Central cholinesterase inhibition enhances glutamatergic. Journal of Neurophysiology. 2010 Apr;103(4):1748-1757. https://doi.org/10.1152/jn.00949.2009
Transmission, Synaptic ; Kozhemyakin, Maxim ; Rajasekaran, Karthik ; Kapur, Jaideep. / Central cholinesterase inhibition enhances glutamatergic. In: Journal of Neurophysiology. 2010 ; Vol. 103, No. 4. pp. 1748-1757.
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