Imperial College London

ProfessorPeterKohl

Faculty of MedicineNational Heart & Lung Institute

Visiting Professor
 
 
 
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Contact

 

p.kohl Website

 
 
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Location

 

Heart Science CentreHarefield Hospital

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Summary

 

Publications

Publication Type
Year
to

313 results found

Peyronnet R, Desai A, Edelmann J-C, Cameron BA, Emig R, Kohl P, Dean Det 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'.

Journal article

Quinn TA, Kohl P, 2022, The Bainbridge effect: stretching our understanding of cardiac pacemaking for more than a century, JOURNAL OF PHYSIOLOGY-LONDON, ISSN: 0022-3751

Journal article

Giardini F, Olianti C, Biasci V, Arecchi G, Zaglia T, Mongillo M, Cerbai E, Zgierski-Johnston C, Kohl P, Sacconi Let al., 2022, Correlating electrical dysfunctions and structural remodeling in Arrhythmogenic Mouse Hearts by advanced optical methods, Publisher: OXFORD UNIV PRESS, ISSN: 0008-6363

Conference paper

Khokhlova A, Solovyova O, Kohl P, Peyronnet Ret 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

Journal article

Emig R, Hoess P, Cai H, Kohl P, Peyronnet R, Weber W, Hoerner Met 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

Journal article

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

Journal article

Duerschmied D, Hilgendorf I, Kohl P, Rog-Zielinska E, Verheyen Jet al., 2022, SFB1425-The heterocellular nature of cardiac lesions: Identities, interactions, implications, KARDIOLOGE, Vol: 16, Pages: 128-135, ISSN: 1864-9718

Journal article

Kohl P, 2022, Ask not what The Journal can do for you, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 1537-1538, ISSN: 0022-3751

Journal article

Rog-Zielinska EA, Kohl P, 2022, Cardiomyocyte t-tubular fluid pumping, Publisher: CELL PRESS, Pages: 155A-155A, ISSN: 0006-3495

Conference paper

Simon-Chica A, Fernandez MC, Wuelfers EM, Lother A, Hilgendorf I, Seemann G, Ravens U, Kohl P, Schneider-Warme Fet 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

Journal article

Greiner J, Schiatti T, Kaltenbacher W, Dente M, Semenjakin A, Kok T, Fiegle DJ, Seidel T, Ravens U, Kohl P, Peyronnet R, Rog-Zielinska EAet 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

Journal article

Yamaguchi Y, Allegrini B, Rapetti-Mauss R, Picard V, Garcon L, Kohl P, Soriani O, Peyronnet R, Guizouarn Het 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

Journal article

Emig R, Zgierski-Johnston CM, Timmermann V, Taberner AJ, Nash MP, Kohl P, Peyronnet Ret 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.

Journal article

Abu Nahia K, Migdal M, Quinn TA, Poon K-L, Lapinski M, Sulej A, Liu J, Mondal SS, Pawlak M, Bugajski L, Piwocka K, Brand T, Kohl P, Korzh V, Winata Cet 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.

Journal article

Ravens U, Kohl P, 2021, Mechanoelectric feedback in the human heart: A causal affair, HEART RHYTHM, Vol: 18, Pages: 1414-1415, ISSN: 1547-5271

Journal article

Rog-Zielinska E, Kohl P, 2021, Nanoscopic t-tubular deformation during cardiac mechanical cycle, Publisher: SPRINGER, Pages: 45-45, ISSN: 0175-7571

Conference paper

Jakob D, Klesen A, Darkow E, Kari FA, Beyersdorf F, Kohl P, Ravens U, Peyronnet Ret 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

Journal article

Jakob D, Klesen A, Allegrini B, Darkow E, Aria D, Emig R, Chica AS, Rog-Zielinska EA, Guth T, Beyersdorf F, Kari FA, Proksch S, Hatem SN, Karck M, Kunzel SR, Guizouarn H, Schmidt C, Kohl P, Ravens U, Peyronnet Ret 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

Journal article

Darkow E, Nguyen TT, Stolina M, Kari FA, Schmidt C, Wiedmann F, Baczko I, Kohl P, Rajamani S, Ravens U, Peyronnet Ret 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

Journal article

Emig R, Knodt W, Krussig MJ, Zgierski-Johnston CM, Gorka O, Gross O, Kohl P, Ravens U, Peyronnet Ret al., 2021, Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing, CELLS, Vol: 10

Journal article

Rog-Zielinska EA, Scardigli M, Peyronnet R, Zgierski-Johnston CM, Greiner J, Madl J, O'Toole ET, Morphew M, Hoenger A, Sacconi L, Kohl Pet al., 2021, Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange, CIRCULATION RESEARCH, Vol: 128, Pages: 203-215, ISSN: 0009-7330

Journal article

Wuelfers EM, Greiner J, Giese M, Madl J, Kroll J, Stiller B, Kohl P, Rog-Zielinska EA, Fuerniss HEet al., 2021, Quantitative collagen assessment in right ventricular myectomies form patients with tetralogy of Fallot, EUROPACE, Vol: 23, Pages: I38-I47, ISSN: 1099-5129

Journal article

Rog-Zielinska EA, Moss R, Kaltenbacher W, Greiner J, Verkade P, Seemann G, Kohl P, Cannell MBet 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

Journal article

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

Journal article

M├╝llenbroich MC, Kelly A, Acker C, Bub G, Bruegmann T, Di Bona A, Entcheva E, Ferrantini C, Kohl P, Lehnart SE, Mongillo M, Parmeggiani C, Richter C, Sasse P, Zaglia T, Sacconi L, Smith GLet al., 2021, Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review., Front Physiol, Vol: 12, ISSN: 1664-042X

Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications. This article, which emerged from the international NOTICE workshop in 2018, reviews the state-of-the-art optical techniques used for cardiac electrophysiological research and the underlying biophysics. The design and performance of optical reporters and optogenetic actuators are reviewed along with limitations of current probes. The physics of light interaction with cardiac tissue is detailed and associated challenges with the use of optical sensors and actuators are presented. Case studies include the use of fluorescence recovery after photobleaching and super-resolution microscopy to explore the micro-structure of cardiac cells and a review of two photon and light sheet technologies applied to cardiac tissue. The emergence of cardiac optogenetics is reviewed and the current work exploring the potential clinical use of optogenetics is also described. Approaches which combine optogenetic manipulation and optical voltage measurement are discussed, in terms of platforms that allow real-time manipulation of whole heart electrophysiology in open and closed-loop systems to study optimal ways to terminate spiral arrhythmias. The design and operation of optics-based approaches that allow high-throughput cardiac electrophysiological assays is presented. Finally, emerging techniques of photo-acoustic imaging and stress sensors are described along with strategies for future development and establishment of these techniques in mainstream electrophysiological research.

Journal article

Haerdtner C, Kornemann J, Krebs K, Ehlert CA, Jander A, Zou J, Starz C, Rauterberg S, Sharipova D, Dufner B, Hoppe N, Dederichs T-S, Willecke F, Stachon P, Heidt T, Wolf D, von zur Muehlen C, Madl J, Kohl P, Kaeser R, Boettler T, Pieterman EJ, Princen HMG, Ho-Tin-Noe B, Swirski FK, Robbins CS, Bode C, Zirlik A, Hilgendorf Iet al., 2020, Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering, BASIC RESEARCH IN CARDIOLOGY, Vol: 115, ISSN: 0300-8428

Journal article

Al-Shammari H, Latif N, Sarathchandra P, McCormack A, Rog-Zielinska EA, Raja S, Kohl P, Yacoub MH, Peyronnet R, Chester AHet al., 2020, Expression and function of mechanosensitive ion channels in human valve interstitial cells., PLoS One, Vol: 15, Pages: e0240532-e0240532, ISSN: 1932-6203

BACKGROUND: The ability of heart valve cells to respond to their mechanical environment represents a key mechanism by which the integrity and function of valve cusps is maintained. A number of different mechanotransduction pathways have been implicated in the response of valve cells to mechanical stimulation. In this study, we explore the expression pattern of several mechanosensitive ion channels (MSC) and their potential to mediate mechanosensitive responses of human valve interstitial cells (VIC). METHODS: MSC presence and function were probed using the patch clamp technique. Protein abundance of key MSC was evaluated by Western blotting in isolated fibroblastic VIC (VICFB) and in VIC differentiated towards myofibroblastic (VICMB) or osteoblastic (VICOB) phenotypes. Expression was compared in non-calcified and calcified human aortic valves. MSC contributions to stretch-induced collagen gene expression and to VIC migration were assessed by pharmacological inhibition of specific channels. RESULTS: Two MSC types were recorded in VICFB: potassium selective and cation non-selective channels. In keeping with functional data, the presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level. Differentiation of VICFB into VICMB or VICOB phenotypes was associated with a lower expression of TREK-1 and Kir6.1, and a higher expression of TRPV4 and TRPC6. Differences in MSC expression were also seen in non-calcified vs calcified aortic valves where TREK-1, TRPM4 and TRPV4 expression were higher in calcified compared to control tissues. Cyclic stretch-induced expression of COL I mRNA in cultured VICFB was blocked by RN-9893, a selective inhibitor of TRPV4 channels while having no effect on the stretch-induced expression of COL III. VICFB migration was blocked with the non-specific MSC blocker streptomycin and by GSK417651A an inhibitor of TRPC6/3. CONCLUSION: Aortic VIC ex

Journal article

Zgierski-Johnston CM, Ayub S, Fernandez MC, Rog-Zielinska EA, Barz F, Paul O, Kohl P, Ruther Pet al., 2020, Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts, PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, Vol: 154, Pages: 51-61, ISSN: 0079-6107

Journal article

MacDonald EA, Madl J, Greiner J, Ramadan AF, Wells SM, Torrente AG, Kohl P, Rog-Zielinska EA, Quinn TAet al., 2020, Sinoatrial node structure, mechanics, electrophysiology and the chronotropic response to stretch in rabbit and mouse, Frontiers in Physiology, Vol: 11, Pages: 1-15, ISSN: 1664-042X

The rhythmic electrical activity of the heart’s natural pacemaker, the sinoatrial node (SAN), determines cardiac beating rate (BR). SAN electrical activity is tightly controlled by multiple factors, including tissue stretch, which may contribute to adaptation of BR to changes in venous return. In most animals, including human, there is a robust increase in BR when the SAN is stretched. However, the chronotropic response to sustained stretch differs in mouse SAN, where it causes variable responses, including decreased BR. The reasons for this species difference are unclear. They are thought to relate to dissimilarities in SAN electrophysiology (particularly action potential morphology) between mouse and other species and to how these interact with subcellular stretch-activated mechanisms. Furthermore, species-related differences in structural and mechanical properties of the SAN may influence the chronotropic response to SAN stretch. Here we assess (i) how the BR response to sustained stretch of rabbit and mouse isolated SAN relates to tissue stiffness, (ii) whether structural differences could account for observed differences in BR responsiveness to stretch, and (iii) whether pharmacological modification of mouse SAN electrophysiology alters stretch-induced chronotropy. We found disparities in the relationship between SAN stiffness and the magnitude of the chronotropic response to stretch between rabbit and mouse along with differences in SAN collagen structure, alignment, and changes with stretch. We further observed that pharmacological modification to prolong mouse SAN action potential plateau duration rectified the direction of BR changes during sustained stretch, resulting in a positive chronotropic response akin to that of other species. Overall, our results suggest that structural, mechanical, and background electrophysiological properties of the SAN influence the chronotropic response to stretch. Improved insight into the biophysical determinants of st

Journal article

Darkow E, Rog-Zielinska EA, Madl J, Brandel A, Siukstaite L, Omidvar R, Kohl P, Ravens U, Roemer W, Peyronnet Ret al., 2020, The lectin LecA sensitizes the human stretch-activated channel TREK-1 but not piezo1 and binds selectively to cardiac non-myocytes, Frontiers in Physiology, Vol: 11, Pages: 1-16, ISSN: 1664-042X

The healthy heart adapts continuously to a complex set of dynamically changing mechanical conditions. The mechanical environment is altered by, and contributes to, multiple cardiac diseases. Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). The precise role of SAC in the heart is unclear, in part because there are few SAC-specific pharmacological modulators. That said, most SAC can be activated by inducers of membrane curvature. The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for P. aeruginosa-induced membrane curvature, resulting in formation of endocytic structures and bacterial cell invasion. We investigate whether LecA modulates SAC activity. TREK-1 and Piezo1 have been selected, as they are widely expressed in the body, including cardiac tissue, and they are “canonical representatives” for the potassium selective and the cation non-selective SAC families, respectively. Live cell confocal microscopy and electron tomographic imaging were used to follow binding dynamics of LecA, and to track changes in cell morphology and membrane topology in human embryonic kidney (HEK) cells and in giant unilamellar vesicles (GUV). HEK cells were further transfected with human TREK-1 or Piezo1 constructs, and ion channel activity was recorded using the patch-clamp technique. Finally, freshly isolated cardiac cells were used for studies into cell type dependency of LecA binding. LecA (500 nM) binds within seconds to the surface of HEK cells, with highest concentration at cell-cell contact sites. Local membrane invaginations are detected in the presence of LecA, both in the plasma membrane of cells (by 17 min of LecA exposure) as well as in GUV. In HEK cells, LecA sensitizes TREK-1, but not Piezo1, to voltage and mechanical stimulation. In freshly isolated cardiac cells, LecA binds to non-myocytes, but not to ventricular or atrial cardiomyocytes. This cell type speci

Journal article

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