A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic

Joukar, Siyavash

doi:10.1186/s42826-021-00102-3

Cited by 39 publications

(17 citation statements)

References 79 publications

(86 reference statements)

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“…14 For a more detailed comparison of ionic currents in different species, the reader is referred to here. 15 As with the AP, there are important species differences in cardiac Ca 2+ handling. For example, mice and rats primarily (>90%) utilize sarcoplasmic reticulum (SR)mediated Ca 2+ cycling (via the cardiac ryanodine receptor [RyR2] and the SR Ca uptake pump [SERCA2a]) for excitation-contraction coupling, whereas in humans, dogs, and rabbits the SR accounts for ≈65%, with the remainder coming from outside the cell via the L-type Ca channel (Ca V 1.2) and the NCX (Na/Ca exchanger).…”

Section: Species Differences In the Cardiac Action Potential And Card...mentioning

confidence: 99%

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Animal Models to Study Cardiac Arrhythmias

2022

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Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide, accounting for 10% to 15% of all deaths. Although most arrhythmias are due to acquired heart disease, inherited channelopathies and cardiomyopathies disproportionately affect children and young adults. Arrhythmogenesis is complex, involving anatomic structure, ion channels and regulatory proteins, and the interplay between cells in the conduction system, cardiomyocytes, fibroblasts, and the immune system. Animal models of arrhythmia are powerful tools for studying not only molecular and cellular mechanism of arrhythmogenesis but also more complex mechanisms at the whole heart level, and for testing therapeutic interventions. This review summarizes basic and clinical arrhythmia mechanisms followed by an in-depth review of published animal models of genetic and acquired arrhythmia disorders.

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Section: Species Differences In the Cardiac Action Potential And Card...mentioning

confidence: 99%

“…14 For a more detailed comparison of ionic currents in different species, the reader is referred to here. 15…”

Section: Principles Of Cardiac Electrophysiologymentioning

confidence: 99%

Animal Models to Study Cardiac Arrhythmias

2022

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“…Most of the studies in CPVT are from small animal models, and mouse has a small heart size and fast heart rate. We need to be aware of the limitations to generalize the results of the small animal research to humans ( Joukar, 2021 ).…”

Section: Dissecting the Antiarrhythmic Mechanisms Of Flecainide In Cpvtmentioning

confidence: 99%

The Antiarrhythmic Mechanisms of Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia

Peng

Lin

et al. 2022

Front. Physiol.

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe yet rare inherited arrhythmia disorder. The cornerstone of CPVT medical therapy is the use of β-blockers; 30% of patients with CPVT do not respond well to optimal β-blocker treatment. Studies have shown that flecainide effectively prevents life-threatening arrhythmias in CPVT. Flecainide is a class IC antiarrhythmic drug blocking cardiac sodium channels. RyR2 inhibition is proposed as the principal mechanism of antiarrhythmic action of flecainide in CPVT, while it is highly debated. In this article, we review the current progress of this issue.

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“…Ion channels are ubiquitous membrane proteins critical to almost all physiological processes, such as muscle contraction, neural transmission, and cardiac pace-maker function [1][2][3]. Ion channels are macromolecules with a relatively long size that are composed of subunits spanning the cell membrane.…”

Section: Introductionmentioning

confidence: 99%

Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs

et al. 2022

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Mutations of ion channels and G-protein-coupled receptors (GPCRs) are not uncommon and can lead to cardiovascular diseases. Given previously reported multiple factors associated with high mutation rates, we sorted the relative mutability of multiple human genes by (i) proximity to telomeres and/or (ii) high adenine and thymine (A+T) content. We extracted genomic information using the genome data viewer and examined the mutability of 118 ion channel and 143 GPCR genes based on their association with factors (i) and (ii). We then assessed these two factors with 31 genes encoding ion channels or GPCRs that are targeted by the United States Food and Drug Administration (FDA)-approved drugs. Out of the 118 ion channel genes studied, 80 met either factor (i) or (ii), resulting in a 68% match. In contrast, a 78% match was found for the 143 GPCR genes. We also found that the GPCR genes (n = 20) targeted by FDA-approved drugs have a relatively lower mutability than those genes encoding ion channels (n = 11), where targeted genes encoding GPCRs were shorter in length. The result of this study suggests that the use of matching rate analysis on factor-druggable genome is feasible to systematically compare the relative mutability of GPCRs and ion channels. The analysis on chromosomes by two factors identified a unique characteristic of GPCRs, which have a significant relationship between their nucleotide sizes and proximity to telomeres, unlike most genetic loci susceptible to human diseases.

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A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic

Cited by 39 publications

References 79 publications

Animal Models to Study Cardiac Arrhythmias

Animal Models to Study Cardiac Arrhythmias

The Antiarrhythmic Mechanisms of Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia

Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs

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