The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals, Drugs, and Solutions Used in This Study
2.2. Cell Culture
2.3. Electrophysiological Measurements
2.4. Data Recordings
2.5. Data Analyses
2.6. Single-Channel Analyses
2.7. Simulation Modeling
2.8. Animal Experiments
2.9. Statistical Analyses
3. Results
3.1. Inhibitory Effect of BRV on the Amplitude of M-Type K+ Current (IK(M))
3.2. Mild Inhibition of BRV on Delayed-Rectifier K+ Current (IK(DR))
3.3. Mild Inhibitory Effect on Hyperpolarization-Activated Cation Current (Ih) Caused by BRV
3.4. Effect of BRV on Voltage-Gated Na+ Current (INa)
3.5. Steady-State Inactivation Curve of Peak INa Taken with or without Addition of BRV
3.6. Stimulatory Effect of BRV on the Activity of Large-Conductance Ca2+-Activated K+ (BKCa) Channels
3.7. Inhibitory Effect of BRV on INa in Hippocampal Neurons
3.8. Effect of BRV on BKCa-Channel Activity Recorded from mHippoE-14 Hippocampal Neurons
3.9. Simulated Firing of Action Potentials (APs) in Modeled Neurons Used to Mimic the Effect of BRV
3.10. Effects of BRV versus LEV on Acute Seizures in Different Animal Models
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Symbol | Description | Value (in Control) | Value (in the Presence of 10 µM BRV) |
---|---|---|---|
Cm | Membrane capacitance (pF) | 1 | 1 |
gNa | Na+ current conductance (mS/cm2) | 35 | 17.5 |
gCa | Ca2+ current conductance (mS/cm2) | 0.08 | 0.08 |
gKDR | Delayed-rectifier K+ current conductance (mS/cm2) | 6.0 | 5.4 |
gA | A-type K+ current conductance (mS/cm2) | 1.4 | 1.4 |
gM | M-type K+ current conductance (mS/cm2) | 1 | 0.7 |
gKCa | Ca2+-activated K+ current conductance (mS/cm2) | 10 | 20 |
gh | Hyperpolarization-activated cation current conductance (mS/cm2) | 0.4 | 0.36 |
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Hung, T.-Y.; Wu, S.-N.; Huang, C.-W. The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability. Biomedicines 2021, 9, 369. https://doi.org/10.3390/biomedicines9040369
Hung T-Y, Wu S-N, Huang C-W. The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability. Biomedicines. 2021; 9(4):369. https://doi.org/10.3390/biomedicines9040369
Chicago/Turabian StyleHung, Te-Yu, Sheng-Nan Wu, and Chin-Wei Huang. 2021. "The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability" Biomedicines 9, no. 4: 369. https://doi.org/10.3390/biomedicines9040369