Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice
Copyright © 2024. Published by Elsevier B.V..
Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:826 |
|---|---|
| Enthalten in: |
Neuroscience letters - 826(2024) vom: 15. März, Seite 137733 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Guang-Gao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.neulet.2024.137733 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369825551 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369825551 | ||
| 003 | DE-627 | ||
| 005 | 20240401232823.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240317s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.neulet.2024.137733 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1359.xml |
| 035 | |a (DE-627)NLM369825551 | ||
| 035 | |a (NLM)38492880 | ||
| 035 | |a (PII)S0304-3940(24)00110-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Guang-Gao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.04.2024 | ||
| 500 | |a Date Revised 01.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cerebellar climbing fiber-Purkinje cell synapses | |
| 650 | 4 | |a Etomidate | |
| 650 | 4 | |a Long-term depression | |
| 650 | 4 | |a NMDA receptor | |
| 650 | 4 | |a Pharmacology | |
| 650 | 4 | |a Protein kinase A | |
| 650 | 4 | |a Whole-cell recording | |
| 650 | 7 | |a Etomidate |2 NLM | |
| 650 | 7 | |a Z22628B598 |2 NLM | |
| 650 | 7 | |a Receptor, Cannabinoid, CB1 |2 NLM | |
| 650 | 7 | |a Cyclic AMP-Dependent Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.11 |2 NLM | |
| 650 | 7 | |a Anesthetics, Intravenous |2 NLM | |
| 700 | 1 | |a Xu, Ying-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ming-Ze |e verfasserin |4 aut | |
| 700 | 1 | |a Bing, Yan-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Wen-Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, De-Lai |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuroscience letters |d 1975 |g 826(2024) vom: 15. März, Seite 137733 |w (DE-627)NLM000386529 |x 1872-7972 |7 nnns |
| 773 | 1 | 8 | |g volume:826 |g year:2024 |g day:15 |g month:03 |g pages:137733 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.neulet.2024.137733 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 826 |j 2024 |b 15 |c 03 |h 137733 | ||