Publications
319 results found
Bailey DM, Berg RMG, Stewart A, et al., 2023, Sharpey-Schafer, Langley and Sherrington: 'swordsmen' of physiology. A historical look to the future., Exp Physiol
Kubo Y, Kohl P, 2023, Congratulations, celebrations, invitations!, J Physiol, Vol: 601
Karoutas A, Szymanski W, Rausch T, et al., 2023, Author Correction: The NSL complex maintains nuclear architecture stability via lamin A/C acetylation., Nat Cell Biol
Chleilat E, Walz TP, Kohl P, et al., 2022, New insights into reperfusion arrhythmia mechanism and means to circumvent perivascular excitation tunnelling-based rhythm disturbance, Publisher: ELSEVIER SCI LTD, Pages: S25-S26, ISSN: 0022-2828
Kohl P, 2022, Opinion matters, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 5169-5169, ISSN: 0022-3751
Peyronnet R, Desai A, Edelmann J-C, et al., 2022, Simultaneous assessment of radial and axial myocyte mechanics by combining atomic force microscopy and carbon fibre techniques., Philos Trans R Soc Lond B Biol Sci, Vol: 377
Cardiomyocytes sense and shape their mechanical environment, contributing to its dynamics by their passive and active mechanical properties. While axial forces generated by contracting cardiomyocytes have been amply investigated, the corresponding radial mechanics remain poorly characterized. Our aim is to simultaneously monitor passive and active forces, both axially and radially, in cardiomyocytes freshly isolated from adult mouse ventricles. To do so, we combine a carbon fibre (CF) set-up with a custom-made atomic force microscope (AFM). CF allows us to apply stretch and to record passive and active forces in the axial direction. The AFM, modified for frontal access to fit in CF, is used to characterize radial cell mechanics. We show that stretch increases the radial elastic modulus of cardiomyocytes. We further find that during contraction, cardiomyocytes generate radial forces that are reduced, but not abolished, when cells are forced to contract near isometrically. Radial forces may contribute to ventricular wall thickening during contraction, together with the dynamic re-orientation of cells and sheetlets in the myocardium. This new approach for characterizing cell mechanics allows one to obtain a more detailed picture of the balance of axial and radial mechanics in cardiomyocytes at rest, during stretch, and during contraction. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.
Quinn TA, Kohl P, 2022, The Bainbridge effect: stretching our understanding of cardiac pacemaking for more than a century, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 4377-4379, ISSN: 0022-3751
Giardini F, Olianti C, Biasci V, et al., 2022, Correlating electrical dysfunctions and structural remodeling in Arrhythmogenic Mouse Hearts by advanced optical methods, Publisher: OXFORD UNIV PRESS, ISSN: 0008-6363
Emig R, Hoess P, Cai H, et al., 2022, Benchmarking of Cph1 Mutants and DrBphP for Light-Responsive Phytochrome-Based Hydrogels with Reversibly Adjustable Mechanical Properties, ADVANCED BIOLOGY, Vol: 6, ISSN: 2701-0198
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- Citations: 1
Kohl P, Greiner J, Rog-Zielinska EA, 2022, Electron microscopy of cardiac 3D nanodynamics: form, function, future, NATURE REVIEWS CARDIOLOGY, Vol: 19, Pages: 607-619, ISSN: 1759-5002
Khokhlova A, Solovyova O, Kohl P, et al., 2022, Single cardiomyocytes from papillary muscles show lower preload-dependent activation of force compared to cardiomyocytes from the left ventricular free wall, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 166, Pages: 127-136, ISSN: 0022-2828
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- Citations: 1
Kohl P, 2022, Ask not what The Journal can do for you, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 1537-1538, ISSN: 0022-3751
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- Citations: 1
Duerschmied D, Hilgendorf I, Kohl P, et al., 2022, SFB1425-The heterocellular nature of cardiac lesions: Identities, interactions, implications, KARDIOLOGIE, Vol: 16, Pages: 128-135, ISSN: 2731-7129
Rog-Zielinska EA, Kohl P, 2022, Cardiomyocyte t-tubular fluid pumping, Publisher: CELL PRESS, Pages: 155A-155A, ISSN: 0006-3495
Simon-Chica A, Fernandez MC, Wuelfers EM, et al., 2022, Novel insights into the electrophysiology of murine cardiac macrophages: relevance of voltage-gated potassium channels, Cardiovascular Research, Vol: 118, Pages: 798-813, ISSN: 0008-6363
AimsMacrophages (MΦ), known for immunological roles, such as phagocytosis and antigen presentation, have been found to electrotonically couple to cardiomyocytes (CM) of the atrioventricular node via Cx43, affecting cardiac conduction in isolated mouse hearts. Here, we characterize passive and active electrophysiological properties of murine cardiac resident MΦ, and model their potential electrophysiological relevance for CM.Methods and resultsWe combined classic electrophysiological approaches with 3D florescence imaging, RNA-sequencing, pharmacological interventions, and computer simulations. We used Cx3creYFP/+1 mice wherein cardiac MΦ are fluorescently labelled. FACS-purified fluorescent MΦ from mouse hearts were studied by whole-cell patch-clamp. MΦ electrophysiological properties include: membrane resistance 2.2±0.1 GΩ (all data mean±SEM), capacitance 18.3±0.1 pF, resting membrane potential −39.6±0.3 mV, and several voltage-activated, outward or inwardly rectifying potassium currents. Using ion channel blockers (barium, TEA, 4-AP, margatoxin, XEN-D0103, and DIDS), flow cytometry, immuno-staining, and RNA-sequencing, we identified Kv1.3, Kv1.5, and Kir2.1 as channels contributing to observed ion currents. MΦ displayed four patterns for outward and two for inward-rectifier potassium currents. Additionally, MΦ showed surface expression of Cx43, a prerequisite for homo- and/or heterotypic electrotonic coupling. Experimental results fed into development of an original computational model to describe cardiac MΦ electrophysiology. Computer simulations to quantitatively assess plausible effects of MΦ on electrotonically coupled CM showed that MΦ can depolarize resting CM, shorten early and prolong late action potential duration, with effects depending on coupling strength and individual MΦ electrophysiological properties, in particular resting membrane potential and presence/absence of
Greiner J, Schiatti T, Kaltenbacher W, et al., 2022, Consecutive-Day Ventricular and Atrial Cardiomyocyte Isolations from the Same Heart: Shifting the Cost-Benefit Balance of Cardiac Primary Cell Research, CELLS, Vol: 11
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- Citations: 2
Muellenbroich MC, Kelly A, Acker C, et al., 2021, Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review, FRONTIERS IN PHYSIOLOGY, Vol: 12
Yamaguchi Y, Allegrini B, Rapetti-Mauss R, et al., 2021, Hereditary Xerocytosis: Differential Behavior of PIEZO1 Mutations in the N-Terminal Extracellular Domain Between Red Blood Cells and HEK Cells, FRONTIERS IN PHYSIOLOGY, Vol: 12, ISSN: 1664-042X
Emig R, Zgierski-Johnston CM, Timmermann V, et al., 2021, Passive myocardial mechanical properties: meaning, measurement, models., Biophys Rev, Vol: 13, Pages: 587-610, ISSN: 1867-2450
Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.
Abu Nahia K, Migdal M, Quinn TA, et al., 2021, Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region, Cellular and Molecular Life Sciences, Vol: 78, Pages: 6669-6687, ISSN: 1420-682X
The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-β, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.
Ravens U, Kohl P, 2021, Mechanoelectric feedback in the human heart: A causal affair, HEART RHYTHM, Vol: 18, Pages: 1414-1415, ISSN: 1547-5271
Rog-Zielinska E, Kohl P, 2021, Nanoscopic t-tubular deformation during cardiac mechanical cycle, Publisher: SPRINGER, Pages: 45-45, ISSN: 0175-7571
Jakob D, Klesen A, Darkow E, et al., 2021, Heterogeneity and Remodeling of Ion Currents in Cultured Right Atrial Fibroblasts From Patients With Sinus Rhythm or Atrial Fibrillation, FRONTIERS IN PHYSIOLOGY, Vol: 12
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- Citations: 3
Jakob D, Klesen A, Allegrini B, et al., 2021, Piezol and BKca channels in human atrial fibroblasts: Interplay and remodelling in atrial fibrillation, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 158, Pages: 49-62, ISSN: 0022-2828
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- Citations: 9
Darkow E, Nguyen TT, Stolina M, et al., 2021, Small Conductance Ca2+-Activated K+ (SK) Channel mRNA Expression in Human Atrial and Ventricular Tissue: Comparison Between Donor, Atrial Fibrillation and Heart Failure Tissue, FRONTIERS IN PHYSIOLOGY, Vol: 12
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- Citations: 6
Emig R, Knodt W, Krussig MJ, et al., 2021, Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing, CELLS, Vol: 10
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- Citations: 20
Rog-Zielinska EA, Scardigli M, Peyronnet R, et al., 2021, Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange, CIRCULATION RESEARCH, Vol: 128, Pages: 203-215, ISSN: 0009-7330
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- Citations: 11
Wuelfers EM, Greiner J, Giese M, et al., 2021, Quantitative collagen assessment in right ventricular myectomies form patients with tetralogy of Fallot, EUROPACE, Vol: 23, Pages: I38-I47, ISSN: 1099-5129
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- Citations: 2
Rog-Zielinska EA, Moss R, Kaltenbacher W, et al., 2021, Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 153, Pages: 86-92, ISSN: 0022-2828
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- Citations: 9
Quinn TA, Kohl P, 2021, CARDIAC MECHANO-ELECTRIC COUPLING: ACUTE EFFECTS OF MECHANICAL STIMULATION ON HEART RATE AND RHYTHM, PHYSIOLOGICAL REVIEWS, Vol: 101, Pages: 37-92, ISSN: 0031-9333
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- Citations: 38
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