High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism
Abstract
:1. Introduction
2. Results
2.1. Diazepam Exhibits Flumazenil-Insensitive Modulation of α1β2γ2, α2β2γ2, and α5β2γ2 GABAARs
2.2. Different BZD Ligands Exhibit Distinct Flumazenil-Insensitive Modulation of Different GABAARs
2.3. Pentylenetetrazol and Fa173 Abolish the Flumazenil-Insensitive Diazepam Effects
2.4. Anesthesia Induced by Diazepam and Midazolam, but Not Zolpidem, Is Resistant to Flumazenil
2.5. Diazepam-Induced Anesthesia Is Antagonized by Pentylenetetrazol and Fa173
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Expression of GABAA Receptors in Xenopus Oocytes
4.3. Two-Electrode Voltage Clamp Electrophysiology
4.4. Mouse Behavioral Test
4.5. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Wang, N.; Lian, J.; Cao, Y.; Muheyati, A.; Yuan, S.; Ma, Y.; Zhang, S.; Yu, G.; Su, R. High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism. Int. J. Mol. Sci. 2022, 23, 42. https://doi.org/10.3390/ijms23010042
Wang N, Lian J, Cao Y, Muheyati A, Yuan S, Ma Y, Zhang S, Yu G, Su R. High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism. International Journal of Molecular Sciences. 2022; 23(1):42. https://doi.org/10.3390/ijms23010042
Chicago/Turabian StyleWang, Na, Jingjing Lian, Yanqing Cao, Alai Muheyati, Shanshan Yuan, Yujie Ma, Shuzhuo Zhang, Gang Yu, and Ruibin Su. 2022. "High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism" International Journal of Molecular Sciences 23, no. 1: 42. https://doi.org/10.3390/ijms23010042