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Study on Cardiac Ion Channels

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 July 2023) | Viewed by 7802

Special Issue Editors

PhyMedExp, Université de Montpellier, 34295 Montpellier, France
Interests: ionic channel; cardiac physiology; omega 3; arrhythmias
Institute of Functional Genomics (IGF), 34094 Montpellier, France
Interests: cardiac development and disease; regeneration; mechanosensitivity; zebrafish; ion channels

Special Issue Information

Dear Colleagues,

Ion channels are transmembrane proteins that allow ions to pass through cellular membranes. They regulate multiple processes and are highly regulated in turn. In cardiomyocytes, excitation–contraction coupling, how electrical activity generated by voltage-dependent ionic channels triggers cell contractions, is a concept that is well understood. However, how ionic channels are able to regulate cardiac functions ranging from heart development to pathology in response to physiological or pathological stimuli requires further investigation. The understanding of how ionic channels regulate or are regulated during these processes is beneficial to discovering novel therapeutic targets.

The current Special Issue aims to highlight the recent advances in understanding the molecular mechanisms involved in the regulation of physiopathological processes by ionic channels and vice versa.  

Dr. Marie Demion
Dr. Adèle Faucherre
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ionic-channel expression and/or function
  • regulation of ionic channel
  • cardiac development
  • cardiac hypertrophy
  • cardiopmyopathies
  • arrhythmias
  • ionic-channel mutation
  • animal models
  • regeneration
  • congenital heart defects

Published Papers (6 papers)

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Research

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21 pages, 3533 KiB  
Article
Pharmacological Screening of Kv7.1 and Kv7.1/KCNE1 Activators as Potential Antiarrhythmic Drugs in the Zebrafish Heart
by Alicia De la Cruz, Xiaoan Wu, Quinn C. Rainer, Irene Hiniesto-Iñigo, Marta E. Perez, Isak Edler, Sara I. Liin and H. Peter Larsson
Int. J. Mol. Sci. 2023, 24(15), 12092; https://doi.org/10.3390/ijms241512092 - 28 Jul 2023
Viewed by 783
Abstract
Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as [...] Read more.
Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. We used high-resolution all-optical electrophysiology on ex vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2), and to a lesser extent, in the absence of E4031. Moreover, we showed that PUFA analogues slightly shortened the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions, although it plays a more important role when the IKr is compromised, as if the IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in the zebrafish heart. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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15 pages, 39073 KiB  
Article
Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus
by Alvaro R. Ruiz-Fernández, Leonardo Campos, Felipe Villanelo, Jose Antonio Garate and Tomas Perez-Acle
Int. J. Mol. Sci. 2023, 24(14), 11397; https://doi.org/10.3390/ijms241411397 - 13 Jul 2023
Viewed by 730
Abstract
This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. [...] Read more.
This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. This investigation reveals a relatively new and underexplored phenomenon: protein-mediated electroporation. Our research focused on the voltage-sensing domain (VSD) of the NaV1.5 sodium cardiac channel in response to nsPEF stimulation. We scrutinized the VSD structures that form pores and thereby contribute to the physical chemistry that governs the defibrillation effect of nsPEF. To do so, we conducted a comprehensive analysis involving the clustering of 142 replicas simulated for 50 ns under nsPEF stimuli. We subsequently pinpointed the representative structures of each cluster and computed the free energy between them. We find that the selected VSD of NaV1.5 forms pores under nsPEF stimulation, but in a way that significant differs from the traditional VSD opening. This study not only extends our understanding of nsPEF and its interaction with protein channels but also adds a new effect to further study. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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21 pages, 3277 KiB  
Article
Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression
by Elisa Darkow, Dilmurat Yusuf, Sridharan Rajamani, Rolf Backofen, Peter Kohl, Ursula Ravens and Rémi Peyronnet
Int. J. Mol. Sci. 2023, 24(13), 10961; https://doi.org/10.3390/ijms241310961 - 30 Jun 2023
Viewed by 1324
Abstract
The cardiac cell mechanical environment changes on a beat-by-beat basis as well as in the course of various cardiac diseases. Cells sense and respond to mechanical cues via specialized mechano-sensors initiating adaptive signaling cascades. With the aim of revealing new candidates underlying mechano-transduction [...] Read more.
The cardiac cell mechanical environment changes on a beat-by-beat basis as well as in the course of various cardiac diseases. Cells sense and respond to mechanical cues via specialized mechano-sensors initiating adaptive signaling cascades. With the aim of revealing new candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) in human hearts for their chamber- and disease-preferential mRNA expression. Based on a meta-analysis of RNA sequencing studies, we compared the mRNA expression levels of MSC in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and from patients in sinus rhythm (underlying diseases: heart failure, coronary artery disease, heart valve disease) or with atrial fibrillation. Our results suggest that a number of MSC genes are expressed chamber preferentially, e.g., CHRNE in the atria (compared to the ventricles), TRPV4 in the right atrium (compared to the left atrium), CACNA1B and KCNMB1 in the left atrium (compared to the right atrium), as well as KCNK2 and KCNJ2 in ventricles (compared to the atria). Furthermore, 15 MSC genes are differentially expressed in cardiac disease, out of which SCN9A (lower expressed in heart failure compared to donor tissue) and KCNQ5 (lower expressed in atrial fibrillation compared to sinus rhythm) show a more than twofold difference, indicative of possible functional relevance. Thus, we provide an overview of cardiac MSC mRNA expression in the four cardiac chambers from patients with different cardiac diseases. We suggest that the observed differences in MSC mRNA expression may identify candidates involved in altered mechano-transduction in the respective diseases. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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8 pages, 1471 KiB  
Communication
Regional Differences in Ca2+ Signaling and Transverse-Tubules across Left Atrium from Adult Sheep
by Caroline Cros, Matthieu Douard, Sebastien Chaigne, Come Pasqualin, Gilles Bru-Mercier, Alice Recalde, Caroline Pascarel-Auclerc, Thomas Hof, Michel Haïssaguerre, Meleze Hocini, Pierre Jaïs, Olivier Bernus and Fabien Brette
Int. J. Mol. Sci. 2023, 24(3), 2347; https://doi.org/10.3390/ijms24032347 - 25 Jan 2023
Cited by 2 | Viewed by 1108
Abstract
Cardiac excitation-contraction coupling can be different between regions of the heart. Little is known at the atria level, specifically in different regions of the left atrium. This is important given the role of cardiac myocytes from the pulmonary vein sleeves, which are responsible [...] Read more.
Cardiac excitation-contraction coupling can be different between regions of the heart. Little is known at the atria level, specifically in different regions of the left atrium. This is important given the role of cardiac myocytes from the pulmonary vein sleeves, which are responsible for ectopic activity during atrial fibrillation. In this study, we present a new method to isolate atrial cardiac myocytes from four different regions of the left atrium of a large animal model, sheep, highly relevant to humans. Using collagenase/protease we obtained calcium-tolerant atrial cardiac myocytes from the epicardium, endocardium, free wall and pulmonary vein regions. Calcium transients were slower (time to peak and time to decay) in free wall and pulmonary vein myocytes compared to the epicardium and endocardium. This is associated with lower t-tubule density. Overall, these results suggest regional differences in calcium transient and t-tubule density across left atria, which may play a major role in the genesis of atrial fibrillation. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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Review

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17 pages, 1473 KiB  
Review
Ion Channels in the Development and Remodeling of the Aortic Valve
by Christophe Simard, Margaux Aize, Sébastien Chaigne, Harlyne Mpweme Bangando and Romain Guinamard
Int. J. Mol. Sci. 2023, 24(6), 5860; https://doi.org/10.3390/ijms24065860 - 20 Mar 2023
Viewed by 1751
Abstract
The role of ion channels is extensively described in the context of the electrical activity of excitable cells and in excitation-contraction coupling. They are, through this phenomenon, a key element for cardiac activity and its dysfunction. They also participate in cardiac morphological remodeling, [...] Read more.
The role of ion channels is extensively described in the context of the electrical activity of excitable cells and in excitation-contraction coupling. They are, through this phenomenon, a key element for cardiac activity and its dysfunction. They also participate in cardiac morphological remodeling, in particular in situations of hypertrophy. Alongside this, a new field of exploration concerns the role of ion channels in valve development and remodeling. Cardiac valves are important components in the coordinated functioning of the heart by ensuring unidirectional circulation essential to the good efficiency of the cardiac pump. In this review, we will focus on the ion channels involved in both the development and/or the pathological remodeling of the aortic valve. Regarding valve development, mutations in genes encoding for several ion channels have been observed in patients suffering from malformation, including the bicuspid aortic valve. Ion channels were also reported to be involved in the morphological remodeling of the valve, characterized by the development of fibrosis and calcification of the leaflets leading to aortic stenosis. The final stage of aortic stenosis requires, until now, the replacement of the valve. Thus, understanding the role of ion channels in the progression of aortic stenosis is an essential step in designing new therapeutic approaches in order to avoid valve replacement. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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Other

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8 pages, 489 KiB  
Opinion
LF Power of HRV Could Be the Piezo2 Activity Level in Baroreceptors with Some Piezo1 Residual Activity Contribution
by Balázs Sonkodi
Int. J. Mol. Sci. 2023, 24(8), 7038; https://doi.org/10.3390/ijms24087038 - 11 Apr 2023
Cited by 2 | Viewed by 1438
Abstract
Heart rate variability is a useful measure for monitoring the autonomic nervous system. Heart rate variability measurements have gained significant demand not only in science, but also in the public due to the fairly low price and wide accessibility of the Internet of [...] Read more.
Heart rate variability is a useful measure for monitoring the autonomic nervous system. Heart rate variability measurements have gained significant demand not only in science, but also in the public due to the fairly low price and wide accessibility of the Internet of things. The scientific debate about one of the measures of heart rate variability, i.e., what low-frequency power is reflecting, has been ongoing for decades. Some schools reason that it represents the sympathetic loading, while an even more compelling reasoning is that it measures how the baroreflex modulates the cardiac autonomic outflow. However, the current opinion manuscript proposes that the discovery of the more precise molecular characteristics of baroreceptors, i.e., that the Piezo2 ion channel containing vagal afferents could invoke the baroreflex, may possibly resolve this debate. It is long known that medium- to high-intensity exercise diminishes low-frequency power to almost undetectable values. Moreover, it is also demonstrated that the stretch- and force-gated Piezo2 ion channels are inactivated in a prolonged hyperexcited state in order to prevent pathological hyperexcitation. Accordingly, the current author suggests that the almost undetectable value of low-frequency power at medium- to high-intensity exercise reflects the inactivation of Piezo2 from vagal afferents in the baroreceptors with some Piezo1 residual activity contribution. Consequently, this opinion paper highlights how low-frequency power of the heart rate variability could represent the activity level of Piezo2 in baroreceptors. Full article
(This article belongs to the Special Issue Study on Cardiac Ion Channels)
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