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Propofol facilitates climbing fiber-Purkinje cell synaptic transmission via NMDA receptor in vitro in mice

Zhang, Xin-Yuan ; Zhang, Yi-Dan ; Cui, Bai-Ri ; Jin, Ri ; Chu, Chun-Ping ; Jin, Xian-Hua ; Qiu, De-Lai

European journal of pharmacology, 2020-11, Vol.887, p.173474-173474, Article 173474 [Periódico revisado por pares]

Netherlands: Elsevier B.V

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Título:
Propofol facilitates climbing fiber-Purkinje cell synaptic transmission via NMDA receptor in vitro in mice
Autor: Zhang, Xin-Yuan ; Zhang, Yi-Dan ; Cui, Bai-Ri ; Jin, Ri ; Chu, Chun-Ping ; Jin, Xian-Hua ; Qiu, De-Lai
Assuntos: Animals ; Cerebellar purkinje cell ; Climbing fiber ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists - pharmacology ; Hypnotics and Sedatives - pharmacology ; Mice ; Mice, Inbred ICR ; NMDA receptor ; Propofol ; Propofol - pharmacology ; Purkinje Cells - drug effects ; Purkinje Cells - physiology ; Receptors, N-Methyl-D-Aspartate - agonists ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - physiology ; Synaptic transmission ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology ; Whole-cell recording
É parte de: European journal of pharmacology, 2020-11, Vol.887, p.173474-173474, Article 173474
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SourceType-Scholarly Journals-1
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Descrição: Propofol is generally used for the induction and maintenance of anesthesia in clinical procedures via activation of γ -aminobutyric acid A (GABAA) receptors. When administered at the clinical dose, propofol use is associated with movement disorders, including dystonia and ataxia, suggesting that propofol administration impacts the function of cerebellar neuronal circuitry. In this study, we investigated the effect of propofol on climbing fiber (CF)-Purkinje cell (PC) synaptic transmission in mouse cerebellar slices in the absence of GABAergic inhibition using a whole-cell recording technique and pharmacological methods. Our results showed that bath application of propofol enhanced CF-PC synaptic transmission, which was demonstrated by an increased amplitude and area under the curve (AUC) of the excitatory postsynaptic currents (EPSCs) accompanied by a decrease in the paired-pulse ratio (PPR). The propofol-induced increase in the amplitude of P1 was concentration-dependent with a half effective concentration (EC50) of 20.9 μM. The propofol-induced increases in the amplitude and AUC of CF-PC EPSCs were abolished by an N-Methyl-D-aspartate (NMDA) receptor blocker. Furthermore, the application of NMDA enhanced CF-PC EPSCs and overwhelmed the effect of propofol on CF-PC EPSCs. Moreover, intracellular blockade of NMDA receptors attenuated the propofol-induced enhancement of CF-PC synaptic transmission but strengthened the propofol-induced change in the PPR. These results indicate that propofol enhances CF-PC synaptic transmission by activation of NMDA receptors in the mouse cerebellar cortex, suggesting that propofol administration might be involved in propofol-induced dysfunction of the cerebellum via NMDA receptors. •Propofol enhanced cerebellar CF-PC EPSCs accompanied with a decrease in PPR.•Effect of propofol on the EPSCs was abolished by extracellular NMDA receptors blocker.•Intracellular blocking NMDA receptors strengthened the propofol-induced decrease in PPR.•Propofol enhanced cerebellar CF-PC EPSCs via NMDA receptors.
Editor: Netherlands: Elsevier B.V
Idioma: Inglês

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Propofol facilitates climbing fiber-Purkinje cell synaptic transmission via NMDA receptor in vitro in mice

Zhang, Xin-Yuan ; Zhang, Yi-Dan ; Cui, Bai-Ri ; Jin, Ri ; Chu, Chun-Ping ; Jin, Xian-Hua ; Qiu, De-Lai

Netherlands: Elsevier B.V

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