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Updated: Aug 9, 2025

Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction
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Spironolactone as a Potential New Treatment to Prevent Arrhythmias in Arrhythmogenic Cardiomyopathy Cell Model

Jean-Baptiste Reisqs1,2, Adrien Moreau2, Yvonne Sleiman2

  • 1Neuromyogene Institute, Claude Bernard University, Lyon 1, 69008 Villeurbanne, France.

Journal of Personalized Medicine
|February 25, 2023
PubMed

Insights

Spironolactone (SP) and canrenoic acid (CA) directly improve cardiac electrical function in arrhythmogenic cardiomyopathy (ACM) models. These drugs normalize action potential duration and calcium handling in patient-derived cells, offering a new therapeutic strategy for ACM.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease causing ventricular arrhythmias.
  • Electrophysiological remodeling, including reduced action potential duration (APD) and disturbed Ca2+ homeostasis, underlies ACM arrhythmias.
  • Mineralocorticoid receptor antagonists like spironolactone (SP) may possess antiarrhythmic properties.

Purpose of the Study:

  • To investigate the direct effects of spironolactone (SP) and canrenoic acid (CA) on cardiomyocytes from an arrhythmogenic cardiomyopathy patient.
  • To assess the impact of SP and CA on electrophysiological parameters and Ca2+ handling in DSC2-mutated hiPSC-CMs.

Main Methods:

  • Utilized human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with a DSC2 gene mutation (c.394C>T, R132C).
  • Assessed the effects of SP and CA on action potential duration (APD), K+ channel currents (hERG, KCNQ1), and intracellular Ca2+ homeostasis.
  • Compared treated hiPSC-CMs with control cells.

Main Results:

  • SP and CA corrected the prolonged APD in DSC2-mutated hiPSC-CMs.
  • These drugs normalized hERG and KCNQ1 K+ channel currents.
  • SP and CA directly improved Ca2+ homeostasis by reducing aberrant Ca2+ events and amplitude.

Conclusions:

  • Spironolactone and canrenoic acid demonstrate direct beneficial effects on the electrophysiology and Ca2+ handling of DSC2-mutated hiPSC-CMs.
  • These findings support a potential new therapeutic strategy targeting ion channel function and Ca2+ dysregulation in arrhythmogenic cardiomyopathy.

Keywords:
arrhythmiasarrhythmogenic cardiomyopathyhiPSC-CMspironolactone

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