HYBRID EVENT: You can participate in person at Madrid, Spain or Virtually from your home or work.

5th Edition of Cardiology World Conference

September 5-7, 2024 | Madrid, Spain

September 05 -07, 2024 | Madrid, Spain
Cardio 2024

Shetuan Zhang

Shetuan Zhang, Speaker at Heart Conferences
Queen’s University, Canada
Title : Protecting cardiac potassium channels as a novel strategy to prevent ischemia-associated arrhythmias and sudden cardiac death

Abstract:

The human ether-a-go-go–related gene (hERG) encodes the potassium channel Kv11.1 (commonly known as hERG) that conducts the rapidly activating delayed rectifier potassium current (IKr). Normal function of hERG is critical for cardiac repolarization and its dysfunction causes long QT syndrome, arrhythmias, and sudden death. Ischemic heart disease is a leading cause of death and about 50% of these fatalities occur suddenly. Prolongation of the QT interval is commonly seen during cardiac ischemia and is a predictor of sudden death in patients with myocardial infarction. However, it is unclear how cardiac ischemia causes QT prolongation. Using rabbit cardiac ischemic model, cell biology, and electrophysiology techniques, we found that 1) Cardiac ischemia activates and increases various proteases including calpain in the extracellular milieu. 2) Proteases such as proteinase K and calpain selectively cleave hERG channels in the extracellular domain (S5-pore linker) of the channel, separating the channel into two fragments and completely abolishing the channel activity. 3) The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, can effectively protect hERG against protease-mediated damage. Since BeKm-1 interferes with the hERG channel function, we created BeKm-1 mutants which have potential to protect hERG without interfering with hERG channel function. In conclusion, hERG is uniquely susceptible to proteases, which may contribute to arrhythmias under conditions such as cardiac ischemia. Protecting hERG channels from proteolytic damage using specific peptides represents a novel strategy to prevent arrhythmia and sudden death in patients with ischemic heart disease.

Biography:

Dr. Shetuan Zhang is a full professor with tenure in the Department of Biomedical and Molecular Sciences at Queen’s University, Kingston, Ontario, Canada. He is a leading expert in the field of heart research and education. He has made significant contributions to our understanding of cardiac potassium channel dysfunction and its role in cardiac arrhythmias and sudden cardiac death. Specifically, his research has revealed how hypokalemia (a reduction in blood potassium level), abuse of drugs such as cocaine and fentanyl, genetic mutations in potassium channels, as well as other medical conditions such as cardiac ischemia can cause arrhythmias and sudden death. His recognitions include the Career Investigator Award from Heart and Stroke Foundation, Ontario, Canada.

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