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Technical Applications of Microelectrode Array and Patch Clamp Recordings on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
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Regulation of Ion Channel Function in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Cancer Cell

Rujia Zhong1, Feng Zhang1, Zhen Yang1

  • 1First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Frontiers in Cardiovascular Medicine
|March 10, 2022
PubMed
Abstract

Insights

Gastrointestinal cancer cell secretions can cause heart rhythm problems (arrhythmias) by disrupting heart cell ion channels. This occurs through DNA methylation changes, offering new insights into cancer-related cardiac dysfunction.

Area of Science:

  • Cardiology
  • Oncology
  • Molecular Biology
  • Electrophysiology

Background:

  • Cardiac dysfunction and arrhythmias are common in cancer patients, often attributed to chemotherapy.
  • Limited research exists on how cancer cell secretions, independent of chemotherapy, affect cardiomyocyte ion channel function.

Purpose of the Study:

  • To investigate the impact of gastrointestinal (GI) cancer cell secretions on ion channel function in human cardiomyocytes.
  • To elucidate the molecular mechanisms underlying cancer-induced cardiac electrophysiological changes.

Main Methods:

  • Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to GI cancer cell medium.
  • Techniques included quantitative polymerase chain reaction (qPCR), patch-clamp electrophysiology, western blotting, immunostaining, and DNA methylation analysis.
  • Investigated the role of transforming growth factor-β (TGF-β) and phosphoinositide 3-kinase (PI3K) signaling pathways.

Main Results:

  • Cancer secretions altered cardiomyocyte action potentials, reducing depolarization velocity and amplitude while prolonging duration.
  • Key ion channel currents (Na+, K+) were significantly affected, with decreased peak and increased late/delayed rectifier currents.
  • Observed changes in ion channel gene expression, increased DNA methylation in promoter regions, and elevated DNA methyltransferases.
  • TGF-β mimicked these effects, while PI3K inhibition attenuated them.

Conclusions:

  • GI cancer cell secretions induce ion channel dysfunction, potentially leading to arrhythmias in cancer patients.
  • This dysfunction may stem from DNA methylation of ion channel genes mediated by TGF-β/PI3K signaling.
  • Findings provide novel insights into the pathogenesis of cancer-related arrhythmias.
Keywords:
DNA methylationarrhythmiacancer cell secretionhuman-induced pluripotent stem cell-derived cardiomyocyteion channel

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