Arrhythmic Risk Assessment of Hypokalaemia Using Human Pluripotent Stem Cell-Derived Cardiac Anisotropic Sheets

Area of Science:

• Cardiovascular Science
• Electrophysiology
• Stem Cell Biology

Background:

• Hypokalaemia (low extracellular K+) is linked to cardiac arrhythmias.
• Previous studies used simpler models; complex human cardiac structures lacked investigation.
• Human ventricular cardiac anisotropic sheets (hvCAS) offer a more complex model.

Purpose of the Study:

• Investigate arrhythmogenicity of hypokalaemia in hvCAS.
• Assess electrophysiological and calcium transient (CaT) changes induced by hypokalaemia.
• Evaluate hvCAS as a platform for arrhythmia research.

Main Methods:

• Human pluripotent stem cell-derived hvCAS were used.
• Optical mapping visualized electrophysiological and CaT changes.
• Experiments were conducted under normokalaemic (5 mM KCl) and hypokalaemic (3 mM KCl) conditions.

Main Results:

• Hypokalaemia increased spontaneous arrhythmias from 0% to 50% (p=0.003).
• Reduced longitudinal and transverse conduction velocity (CV).
• Prolonged action potential duration (APD90), increased action potential and CaT amplitude, and shortened effective refractory periods.

Conclusions:

• Hypokalaemia induces pro-arrhythmic effects in hvCAS.
• Observed changes include altered CV, repolarization, refractoriness, and calcium handling.
• hvCAS serve as a valuable platform for studying electrophysiological substrates and screening arrhythmias.