Genesis of Cardiac Arrhythmias Mike Hansen Biology Department Eastern CT State University.
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Transcript of Genesis of Cardiac Arrhythmias Mike Hansen Biology Department Eastern CT State University.
![Page 1: Genesis of Cardiac Arrhythmias Mike Hansen Biology Department Eastern CT State University.](https://reader033.fdocuments.us/reader033/viewer/2022051819/5515159a550346c77d8b4ce3/html5/thumbnails/1.jpg)
Genesis of Cardiac Arrhythmias
Mike Hansen
Biology Department
Eastern CT State University
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Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias
The Journal of Biological Chemistry Vol. 276, pp. 28,197-28,2003
C. A. Ufret-Vincenty, D. J. Baro, W. J. Lederer, H. A. Rockman, L. E. Quinones, and L. F. Santana
University of Puerto Rico, University of Maryland School of Medicine, and Duke University Medical Center
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Cardiac arrhythmias
• Leading cause of death in patients with HF
• Contractile dysfunction
• Possibly due to prolonged AP:
• Change in ion currents and Ca+ signaling
• Is it deglycosylation?
?
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Methods
• Used a mouse as a model for HF
• It lacked expression of MLP
• Compared with normal heart
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Ventricular myocytes
•ECG measurements
•Single cell a.p.
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Ion channels
•Ion channels in cell membrane•Receive signal to open
•Influx of sodium ions
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Action potential
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Results
•ECG: longer QT intervals in MLP than WT (control)
•Shows MLP is abnormal
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•AP of MLP and WT
•Reveals a.p. were longer in MLP
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Sodium channels• Current-voltage
relationship for sodium channels
• MLP• WT
•Indicates lower Na channel density in MLP
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Voltage dependence for Na channel inactivation
• Slowing of inactivation of channels in MLP
• How are theses changes produced?
• Changes sufficient enough to produce a.p. changes?
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Expression of Na channels
•Western blot •Electrophoresis
• alpha subunit of channel
• reduction in band in MLP relative to WT
• due to heavy glycosylation•MLP less glycosylated
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Lack of Deglycosylation?
• MLP and WT exposed to neuroaminadase
?
• Reduces extracellular glycosylation
• Results on WT were similar to that of HF
• Glycosylation alters channels in HF
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Conclusion
• Altered a.p. play a role in arrhythmias
• Likely due to glycosylation of Na channels
• Neuroamindase effects on WT
• Good for mice, what about humans?
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