Modulation of Redox-Sensitive Cardiac Ion Channels

Authors

Rawan S. Orfali, Imam Mohammad Ibn Saud Islamic University (IMSIU)
Al Hassan Gamal el-din, Chapman University
Varnika Karthik, Chapman University
Elisanjer Lamis, Chapman University
Vanna Xiao, Chapman University
Alena Ramanishka, Chapman University
Abdullah Alwatban, Imam Mohammad Ibn Saud Islamic University (IMSIU)
Osama Alkhamees, Imam Mohammad Ibn Saud Islamic University (IMSIU)
Ali Alaseem, Imam Mohammad Ibn Saud Islamic University (IMSIU)
Young-Woo Nam, Chapman UniversityFollow
Miao Zhang, Chapman UniversityFollow

Document Type

Article

Publication Date

7-8-2025

Abstract

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction.

Comments

This article was originally published in Antioxidants, volume 14, issue 7, in 2025. https://doi.org/10.3390/antiox14070836

Recommended Citation

Orfali, R.; Gamal El-Din, A.H.; Karthick, V.; Lamis, E.; Xiao, V.; Ramanishka, A.; Alwatban, A.; Alkhamees, O.; Alaseem, A.; Nam, Y.-W.; et al. Modulation of Redox-Sensitive Cardiac Ion Channels. Antioxidants 2025, 14, 836. https://doi.org/10.3390/antiox14070836

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This work is licensed under a Creative Commons Attribution 4.0 License.