Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

Yung-Nan Tsai1,2, Ya-Wen Hsiao2, Shien-Fong Lin3

  • 1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Insights

Interleukin-17 (IL-17) disrupts intracellular calcium handling, prolonging action potential duration and increasing susceptibility to ventricular arrhythmias (VA). This mechanism highlights IL-17

Area of Science:

  • Cardiovascular Physiology
  • Electrophysiology
  • Molecular Cardiology

Background:

  • The precise mechanisms by which Interleukin-17 (IL-17) contributes to ventricular arrhythmias (VA) are not fully understood.
  • Investigating the role of intracellular calcium (Cai) handling in IL-17-induced VA is crucial for understanding cardiac arrhythmogenesis.

Purpose of the Study:

  • To elucidate the impact of IL-17 on intracellular calcium handling and its subsequent effect on ventricular arrhythmia susceptibility.
  • To examine the electrophysiological consequences of IL-17 exposure in isolated rabbit hearts.

Main Methods:

  • Utilized optical mapping to assess electrophysiological properties in isolated perfused rabbit hearts exposed to IL-17.
  • Measured action potential duration (APD) and Cai transient duration (CaiTD), and analyzed ion channel mRNA expression via RT-PCR.
  • Compared hearts treated with IL-17, IL-17 with neutralizer, and baseline controls.

Main Results:

  • IL-17 exposure led to prolonged APD80 and CaiTD80, with increased thresholds for alternans and VA induction.
  • Ventricular fibrillation analysis revealed a higher number of phase singularities and dominant frequency in the IL-17 group.
  • Observed upregulation of Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor mRNA, alongside downregulation of L-type Ca2+ current and SERCA2a.

Conclusions:

  • IL-17 exacerbates CaiTD and APD alternans by disrupting cardiac calcium handling mechanisms.
  • These calcium handling disturbances induced by IL-17 significantly increase susceptibility to ventricular arrhythmias.

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