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

Action potential

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?

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