Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome
Abstract
:1. Introduction
2. Results
2.1. Delayed Ventricular Repolarization in Mecp2Null/Y Mice
2.2. Late Sodium Current, INa,Late, Enhancement in Mecp2Null/Y Mice
2.3. Alterations to Fast INa in Mecp2Null/Y Mice
2.4. Effects of the INa,Late Inhibitors Ranolazine and Eleclazine (GS-6615)
3. Discussion
3.1. Summary of Main Findings
3.2. QT Interval and AP Prolongation
3.3. Changes to Fast INa and INa,Late
3.4. Actions of Ranolazine and GS-6615
3.5. Limitations and Conclusions
4. Materials and Methods
4.1. Mouse Model of RTT Used
4.2. Electrocardiogram (ECG) Measurement
4.3. Unrestrained Whole Body Plethysmography
4.4. Ventricular Myocyte Isolation
4.5. Cellular Electrophysiology
4.6. Action Potential (AP) Measurement
4.7. INa,Late Measurement
4.8. INa Measurement
4.9. Data Analysis and Statistics
4.10. Drugs
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Parameter | WT | Mecp2Null/Y | t-Test p Value |
---|---|---|---|
RR (ms) | 130.7 ± 2.4 | 125.8 ± 5.3 | 0.4132 |
HR (bpm) | 460.8 ± 8.6 | 485.8 ± 19.3 | 0.2569 |
PR (ms) | 38.4 ± 0.8 | 36.4 ± 1.0 | 0.1271 |
QRS (ms) | 10.8 ± 0.2 | 12.2 ± 0.5 | 0.0094 |
QT (ms) | 51.9 ± 0.9 | 56.9 ± 1.8 | 0.0233 |
QTc (ms; Equation (1)) | 45.5 ± 0.9 | 50.8 ± 1.0 | 0.0006 |
QTc (ms; Equation (2)) | 64.4 ± 1.1 | 71.0 ± 1.1 | 0.0005 |
Respiratory rate (bpm) | 136.7 ± 4.7 | 104.3 ± 8.2 | 0.0029 |
Parameter | WT | Mecp2Null/Y |
---|---|---|
Resting potential (mV) | 72.2 ± 0.8 | −69.5 ± 0.9 * |
Overshoot (mV) | 48.0 ± 2.0 | 45.4 ± 2.2 |
Amplitude (mV) | 120.2 ± 2.4 | 115.0 ± 2.8 |
Vmax (V s−1) | 139.8 ± 6.1 | 128.1 ± 7.7 |
APD10 (ms) | 0.6 ± 0.1 | 0.8 ± 0.2 |
APD25 (ms) | 2.1 ± 0.4 | 2.5 ± 0.3 |
APD50 (ms) | 6.7 ± 1.1 | 8.1 ± 0.9 |
APD75 (ms) | 71.1 ± 8.2 | 99.6 ± 7.9 * |
APD90 (ms) | 115.6 ± 9.5 | 166.0 ± 10.8 ** |
APD90-APD25 (ms) | 113.5 ± 9.4 | 163.5 ± 10.8 ** |
Threshold stimulus (pA) | 907.4 ± 40.9 | 597.4 ± 29.3 ** |
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Cheng, H.; Charles, I.; James, A.F.; Abdala, A.P.; Hancox, J.C. Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome. Int. J. Mol. Sci. 2022, 23, 5735. https://doi.org/10.3390/ijms23105735
Cheng H, Charles I, James AF, Abdala AP, Hancox JC. Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome. International Journal of Molecular Sciences. 2022; 23(10):5735. https://doi.org/10.3390/ijms23105735
Chicago/Turabian StyleCheng, Hongwei, Ian Charles, Andrew F. James, Ana P. Abdala, and Jules C. Hancox. 2022. "Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome" International Journal of Molecular Sciences 23, no. 10: 5735. https://doi.org/10.3390/ijms23105735