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World J Diabetes. Jan 15, 2021; 12(1): 1-18
Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.1
Diabetes-induced changes in cardiac voltage-gated ion channels
Nihal Ozturk, Serkan Uslu, Semir Ozdemir
Nihal Ozturk, Serkan Uslu, Semir Ozdemir, Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya 07058, Turkey
Author contributions: Ozdemir S designed the study and wrote the manuscript; Uslu S and Ozturk N collected the data and drafted the review article.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Semir Ozdemir, PhD, Professor, Department of Biophysics, Akdeniz University Faculty of Medicine, Dumlupınar Boulevard, Antalya 07058, Turkey.
Received: June 25, 2020
Peer-review started: June 25, 2020
First decision: October 23, 2020
Revised: November 5, 2020
Accepted: November 13, 2020
Article in press: November 13, 2020
Published online: January 15, 2021

Diabetes mellitus affects the heart through various mechanisms such as microvascular defects, metabolic abnormalities, autonomic dysfunction and incompatible immune response. Furthermore, it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy (DCM) in the absence of coronary artery disease. As DCM progresses it causes electrical remodeling of the heart, left ventricular dysfunction and heart failure. Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients. In recent studies, significant changes in repolarizing K+ currents, Na+ currents and L-type Ca2+ currents along with impaired Ca2+ homeostasis and defective contractile function have been identified in the diabetic heart. In addition, insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients. There are many diagnostic tools and management options for DCM, but it is difficult to detect its development and to effectively prevent its progress. In this review, diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.

Keywords: Diabetes, Action potential, Cardiac ion channels, L-type Ca2+ channels, Potassium channels, Sodium channels

Core Tip: Diabetes mellitus is a multisystemic disease that affects many organs. It causes diabetic cardiomyopathy (DCM) in the heart which is a distinctive pathology that occurs independent of vascular complications. In DCM, altered action potential morphology and contractile dysfunction are mostly associated with defective cardiac ion channels such as voltage-gated K+, Na+ and Ca2+ channels. Therefore, with therapeutic agents specific to cardiac ion channels, both arrhythmogenic events and other functional problems can be mitigated in the diabetic heart.