About

Isabelle Deschenes, PhD, is a Professor of Physiology and Cell Biology at The Ohio State University College of Medicine, where she also serves as Chair of the Department of Physiology and Cell Biology. Her research focuses on the molecular basis of cardiac arrhythmias, studying the fundamental molecules that underlie the electrical function of the heart, including ion channels and their accessory subunits. Her work investigates how regulation and dysregulation of inward and outward ion currents contribute to various clinically relevant cardiac arrhythmias, including inherited channelopathies and arrhythmias associated with acquired diseases such as heart failure. Dr. Deschenes utilizes electrophysiological, biochemical, molecular, and imaging techniques to explore the involvement of ion channels in arrhythmias. Her research includes elucidating mechanisms of incomplete penetrance in inherited cardiac channelopathies through the use of patient-specific induced pluripotent stem cells to identify modifier genes. She has also made fundamental contributions to understanding sodium channel structure, assembly, and trafficking. Additionally, her research investigates ion channel remodeling in heart failure, with a particular focus on the role of KChIP2 in regulating cardiac excitability through multiple mechanisms, including transcriptional repression of cardiac genes and microRNAs.

Research topics

• Biophysics
• Internal medicine
• Chemistry
• Biochemistry
• Medicine
• Biology
• Cell biology
• Physical therapy

Selected publications

• PO-04-227 IMPACT OF G-PROTEIN-GATED INWARDLY RECTIFYING POTASSIUM (GIRK) SUBUNIT COMPOSITION ON ACETYLCHOLINE-ACTIVATED POTASSIUM CHANNEL (KACH) FUNCTION

  Heart Rhythm · 2026-04-01

  article
  PublisherDOI

• JNK2 Is a Stress Integrator Driving Atrial Fibrillation Pathogenesis in Aging via Gut-Heart Crosstalk

  Circulation · 2026-04-20

  articleOpen access

  BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and is associated with high morbidity and mortality, particularly in the aging population. Current treatment and prevention strategies remain suboptimal, highlighting the urgent need to better understand the mechanisms underlying aging-associated AF. We recently reported a causal role of the stress-activated kinase JNK2 (c-Jun N-terminal kinase 2) in aging-associated AF pathogenesis, mediated by JNK2-driven sarcoplasmic reticulum Ca 2 + dysfunction. However, the mechanisms by which cardiac JNK2 is activated during aging to promote AF remain unclear. Emerging evidence suggests that interorgan crosstalk contributes critically to the development of cardiovascular diseases. A hyperpermeable gastrointestinal epithelial barrier (“leaky gut”), commonly observed in aged individuals, is associated with elevated levels of proinflammatory cytokines and an increased risk of AF. Although proinflammatory cytokines have been proposed as predisposing factors for AF, clinical and experimental studies have yielded inconsistent results, underscoring the complexity of inflammation-associated AF pathogenesis. Here, we investigated whether cardiac JNK2 integrates diverse stress stimuli, including proinflammatory cytokines and lipopolysaccharide, to drive AF pathogenesis. METHODS: We used aged mice, intestinal epithelium–specific tight junction OD (occludin) knockdown (OD +/− ) mice, and a well-established dextran sulfate sodium–induced leaky gut mouse model characterized by reduced gastrointestinal epithelial occludin expression. A series of physiological and molecular approaches was applied to assess cardiac and gastrointestinal responses. RESULTS: We found that leaky gut significantly activates atrial JNK2, which, in turn, drives Ca 2 + -triggered arrhythmic activity and increases AF inducibility in aged, dextran sulfate sodium–treated, and OD +/− mouse models. Restoration of gut barrier function in dextran sulfate sodium mice, a clinically relevant model, reduced AF susceptibility. Similarly, either JNK2 inhibition or TNF-α (tumor necrosis factor α) blockade abolished the increased AF risk associated with leaky gut. Furthermore, we demonstrate, for the first time, that leaky gut–associated proinflammatory cytokines, including TNF-α and IL-17A (interleukin-17A), together with lipopolysaccharide, activate cardiac JNK2. This activation promotes AF pathogenesis through JNK2-mediated arrhythmogenic mechanisms, including diastolic sarcoplasmic reticulum Ca 2 + leak, Ca 2 + waves, and delayed afterdepolarizations. CONCLUSION: Activated JNK2 functions as a pathological nodal integrator of leaky gut–associated stress signals, mediating gut-to-heart crosstalk and driving inflammation-induced AF pathogenesis. Targeting JNK2 may represent a novel therapeutic strategy for AF.

  PublisherOA PDFDOI

• The two-pore K⁺ channel TREK-1 regulates pressure overload-induced cardiac remodeling

  American Journal of Physiology-Heart and Circulatory Physiology · 2025-05-19 · 3 citations

  articleOpen access

  A major finding of this study is the involvement of the background K + channel TREK-1 in modulating STAT3 activation, profibrotic gene expression, and fibrosis with implications for the cardiac remodeling response to chronic pressure overload.

  PublisherDOI

• Pharmacological Enhancement of Small Conductance Ca ²⁺ -Activated K ⁺ Channels Suppresses Cardiac Arrhythmias in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia

  Circulation Research · 2025-05-29 · 6 citations

  article

  BACKGROUND: Sarcolemmal small conductance Ca 2+ -activated K + channels have the unique capacity to translate intracellular Ca 2+ signal into repolarization, while mitochondrial SK channels can link Ca 2+ cycling to mitochondrial function. We hypothesize that pharmacological enhancement of SK channels can be protective against malignant cardiac arrhythmias associated with disturbances in Ca 2+ handling machinery. METHODS: A mouse CASQ2 KO (calsequestrin type 2 knockout) model of catecholaminergic polymorphic ventricular tachycardia (CPVT) was used for in vivo ECG recordings and for cell electrophysiology, Ca 2+ , and reactive oxygen species imaging in isolated ventricular myocytes (VMs). RESULTS: Bidirectional and polymorphic ventricular tachycardias in CASQ2 KO mice induced by stress challenge (epinephrine+caffeine cocktail) were attenuated by injection of NS309, a specific SK channel enhancer. Voltage-clamp experiments in isolated VMs treated with β-adrenergic agonist isoproterenol showed a reduction of sarcolemmal SK channel current (I SK ) density in CPVT VMs. Application of NS309 to CPVT VMs increased I SK . Current-clamp experiments demonstrated a significant reduction of arrhythmogenic delayed afterdepolarizations and spontaneous Ca 2+ waves in isoproterenol-challenged CPVT VMs pretreated with NS309. Importantly, subsequent application of membrane-impermeable SK channel inhibitor apamin did not reverse the protective effects of NS309, suggesting important roles of mitochondrial SK channels in intracellular Ca 2+ handling rescue. SK channel enhancement reversed the increased rate of reactive oxygen species production by mitochondria in CPVT VMs. It also reversed increased cardiac RyR2 (ryanodine receptor 2) oxidation measured in samples from CPVT hearts of the animals after the stress challenge. Electron microscopy studies showed a significant widening of mitochondria cristae in the ventricular tissue from CPVT mice, which led to a decrease in quaternary supercomplexes of electron transport chain, resulting in impairment of ATP production in VMs under β-adrenergic stimulation. Application of NS309 facilitated cristae flattening in CPVT ventricular tissue and restored supercomplexes and ATP production in VMs from diseased animals. CONCLUSIONS: Sarcolemmal SK channel enhancement reduces arrhythmic potential by restoring repolarization force in CPVT VMs. Activation of mitochondrial SK channels attenuates mitochondria structural changes in CPVT, restoring more efficient electron transport chain assembly into supercomplexes and reducing mito-reactive oxygen species production. This decreases RyR2 oxidation and thus channel activity, reducing spontaneous Ca 2+ waves underlying arrhythmogenic delayed afterdepolarizations.

  PublisherDOI

• Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice

  Communications Medicine · 2025-07-31 · 2 citations

  articleOpen access

  Transthoracic echocardiography remains the primary non-invasive method for assessing cardiac function in clinical practice. However, technical challenges in acquiring accurate apical 4-chamber-long-axis (A4CLAX) views have historically limited mouse studies to left ventricle (LV) assessment using parasternal short-axis (SAX) M-mode imaging. To overcome this limitation, we developed an A4CLAX imaging approach for mice and performed a comparative analysis with established echocardiographic methods to assess cardiac function in healthy mouse hearts. To evaluate the utility of A4CLAX in detecting disease progression, we longitudinally monitored cardiac function of C57BL/6 N mice (male and female) following severe transverse aortic constriction (TAC), using both long-axis biplane (LAX-BP) and conventional SAX M-mode assays. Here we show that LAX-BP echocardiography demonstrates volumetric accuracy comparable to cardiac magnetic resonance (CMR) and detects significant LV functional decline within the first week post-TAC–changes that are not clearly captured by M-mode imaging. Importantly, A4CLAX further enables clinically relevant Doppler assessments, allowing detection of mitral valve regurgitation, restrictive filling patterns, and desynchronized valve motion. It also facilitates right ventricle (RV) functional evaluation and improved atrial visualization, revealing progressive enlargement of the left atrial (LA) and left atrial appendage (LAA) associated with worsening diastolic function. The A4CLAX imaging approach provides clinically comparable, comprehensive echocardiographic evaluation in murine models and offers improved sensitivity for detecting subtle changes in cardiac performance during disease progression. Echocardiography is a non-invasive imaging method commonly used to check heart function in people. However, it has been hard to get clear echocardiographic images of all heart chambers in mice. We imaged mouse hearts from a different direction in healthy mice and in a disease model that mimics heart pressure overload. Our method provided more accurate and detailed information than traditional techniques. It also allowed us to detect heart problems early, including valve issues and changes in heart chamber size and function. Our imaging method could be used to study heart disease and test treatments in mice, ultimately improving treatments for people. Kacira et al. develop an apical 4-chamber-long-axis (A4CLAX) echocardiographic imaging approach for mice. They demonstrate that the A4CLAX method provides clinically comparable and comprehensive evaluation of cardiac function in murine models, with the sensitivity to detect subtle changes in cardiac performance during disease progression.

  PublisherOA PDFDOI

• Transformative Potential of Induced Pluripotent Stem Cells in Congenital Heart Disease Research and Treatment

  Children · 2025-05-23 · 7 citations

  reviewOpen access

  Congenital heart disease (CHD), the most common congenital anomaly, remains a significant lifelong burden despite advancements in medical and surgical interventions. Induced pluripotent stem cells (iPSCs) have emerged as a groundbreaking platform in CHD research, offering patient-specific models to investigate the genetic, epigenetic, and molecular mechanisms driving the disease. Utilizing technologies such as CRISPR/Cas9 gene editing, cardiac organoids, and high-throughput screening, iPSCs enable innovative strategies in disease modeling, precision drug discovery, and regenerative therapies. However, clinical translation faces challenges related to immaturity, differentiation variability, large-scale feasibility, and tumorigenicity. Addressing these barriers will require standardized protocols, bioengineering solutions, and interdisciplinary collaboration. This review examines the critical role of iPSCs in advancing CHD research and care, demonstrating their potential to revolutionize treatment through patient-specific, regenerative approaches. By addressing current limitations and advancing iPSC technology, the field is positioned to pave the way for precision-based CHD therapies for this lifelong condition.

  PublisherOA PDFDOI

• BPS2025 - MicroRNA-1 regulates glucose metabolism via biophysical modulation of ATP-sensitive potassium channel

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Age-Associated Perinexal Narrowing Masks Consequences of Sodium Channel Gain of Function in Guinea Pig Hearts

  JACC. Clinical electrophysiology · 2025-03-05 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Structural and Functional Mechanisms Underlying Activation Gate Dynamics and IFM Motif Accessibility in Human Na _v 1.5

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-04

  preprintOpen access

  Abstract Voltage-gated sodium channels are vital for regulating excitability in muscle and nerve cells, and their dysregulation is linked to a range of diseases. However, therapeutic targeting of Na v channels remains challenging due to a limited understanding of their gating mechanisms. Here, we present a cryo-EM structure of human Na v 1.5 in an intermediate open state, stabilized by interactions between the N-terminal domain and the S6 I segment. This structure reveals a previously uncharacterized Na + binding site adjacent to the conserved inactivation (IFM) motif. Molecular dynamics simulations demonstrate that monovalent cations stably occupy this site, while electrophysiological recordings demonstrate that ion binding modulates IFM motif docking and fast inactivation kinetics. Our findings reveal that IFM accessibility is dynamically regulated in this intermediate state, challenging the canonical hinged-lid model of fast inactivation. Collectively, our study provides a revised structural framework for Na v 1.5 gating mechanisms, suggesting an alternative pathway for ion accessibility that may inform better mechanistic and therapeutic strategies for treating Na v 1.5-related cardiac arrhythmias.

  PublisherOA PDFDOI

• The Role of Global Longitudinal Strain in Detecting Early Left Ventricular Dysfunction in Pediatric Bicuspid Aortic Valve Patients

  Children · 2025-06-06

  editorialOpen access

  Global longitudinal strain (GLS), assessed via speckle tracking echocardiography (STE), is increasingly recognized as a sensitive and early indicator of left ventricular (LV) dysfunction in pediatric patients with bicuspid aortic valve (BAV) [...].

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21GM079467

  NIH · $425k · 2011

• Biophysical Modulation of Cardiac Ion Channels by MicroRNA

  NIH · $4.5M · 2017–2027

• Sodium Channels and Cardiac Arrhythmias

  NIH · $4.0M · 2010–2024

• Cardiac Ion Channel Regulation

  NIH · $3.6M · 2010–2023

• Genotype-Phenotype Discordance in Long QT Syndrome

  NIH · $2.2M · 2014–2019

Frequent coauthors

• Xiaoping Wan

  Shanghai First Maternity and Infant Hospital

  62 shared

• Eckhard Ficker

  51 shared

• Kenneth R. Laurita

  MetroHealth

  47 shared

• Steven Poelzing

  Virginia Tech

  42 shared

• Drew Nassal

  The Ohio State University Wexner Medical Center

  38 shared

• Ji‐Dong Fu

  The Ohio State University

  35 shared

• Jérôme Clatot

  Children's Hospital of Philadelphia

  33 shared

• Krekwit Shinlapawittayatorn

  Chiang Mai University

  30 shared