Presentation on theme: "Genesis of Cardiac Arrhythmias Mike Hansen Biology Department Eastern CT State University."— Presentation transcript:
Genesis of Cardiac Arrhythmias Mike Hansen Biology Department Eastern CT State University
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
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? ?
Methods Used a mouse as a model for HF It lacked expression of MLP Compared with normal heart
Ventricular myocytes ECG measurements Single cell a.p.
Ion channels Ion channels in cell membrane Receive signal to open Influx of sodium ions
Results ECG: longer QT intervals in MLP than WT (control) Shows MLP is abnormal
AP of MLP and WT Reveals a.p. were longer in MLP
Sodium channels Current-voltage relationship for sodium channels MLP WT Indicates lower Na channel density in MLP
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?
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
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
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?