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BS5 Effects of hypokalaemia on electrophysiological and calcium handling of human pluripotent stem cell-derived cardiac anisotropic sheets
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  1. Bimal Gurung
  1. The Chinese University of Hong Kong, Sha Tin, Hong Kong (China)

Abstract

Introduction Hypokalaemia, defined as extracellular concentration [K+] below 3.5 mM, can cause cardiac arrhythmias by triggered or reentrant mechanisms. Whilst these effects have been reported in animal and human stem cell-based models, to date there has been no investigation in more complex structures such as the human ventricular cardiac anisotropic sheet (hvCAS). Here, we investigated arrhythmogenicity, electrophysiological and calcium transient changes induced by hypokalaemia using this bioengineered platform.

Methods An optical mapping technique was applied on hvCAS derived from human pluripotent stem cells to visualize electrophysiological and calcium transient changes under normokalaemic (5mM KCl) and hypokalaemic (3mM KCl) conditions.

Results Hypokalaemia significantly increased the proportion of preparations showing spontaneous arrhythmias from 0/14 to 7/14 (Fisher’s exact test, P=0.003) (figure 1D). Hypokalaemia reduced longitudinal conduction velocity (CV) from 7.81 to 7.18 cms–1 (n = 9-7; P=0.036), transverse CV from 5.72 to 4.69 cms–1 (n = 12-11; P=0.030), prolonged action potential at 90% repolarization (APD90) from 83.46 to 97.45 ms (n = 13-15; P<0.001), increased action potential amplitude from 0.888 to 1.195 ΔF (n = 12-14; P<0.001) and calcium transient amplitude from 0.76 to 1.37 ΔF (n = 12-13; P<0.001), and shortened effective refractory periods from 233 to 173 ms (n = 16-14; P=0.038). Figure 1 (A), (B) and (C) show the representative tracings and isochronal maps of normokalaemic and hypokalaemic samples.

Conclusions Hypokalaemia exerts pro-arrhythmic effects on hvCAS, which are associated with alterations in conduction velocity, repolarization, refractoriness and calcium handling. These preparations can provide a useful platform for investigating electrophysiological substrates and for arrhythmia screening.

Conflict of Interest None

  • Stem Cells
  • Ventricular arrhythmias
  • Hypokalaemia

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