Imperial College London
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ProfessorPeterKohl

Faculty of Medicine, National 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

Citation

BibTex format

@article{Simon-Chica:2022:cvr/cvab126,
author = {Simon-Chica, A and Fernandez, MC and Wuelfers, EM and Lother, A and Hilgendorf, I and Seemann, G and Ravens, U and Kohl, P and Schneider-Warme, F},
doi = {cvr/cvab126},
journal = {Cardiovascular Research},
pages = {798--813},
title = {Novel insights into the electrophysiology of murine cardiac macrophages: relevance of voltage-gated potassium channels},
url = {http://dx.doi.org/10.1093/cvr/cvab126},
volume = {118},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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
AU  - Simon-Chica,A
AU  - Fernandez,MC
AU  - Wuelfers,EM
AU  - Lother,A
AU  - Hilgendorf,I
AU  - Seemann,G
AU  - Ravens,U
AU  - Kohl,P
AU  - Schneider-Warme,F
DO  - cvr/cvab126
EP  - 813
PY  - 2022///
SN  - 0008-6363
SP  - 798
TI  - Novel insights into the electrophysiology of murine cardiac macrophages: relevance of voltage-gated potassium channels
T2  - Cardiovascular Research
UR  - http://dx.doi.org/10.1093/cvr/cvab126
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000755476200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/cardiovascres/article/118/3/798/6212648
UR  - http://hdl.handle.net/10044/1/95490
VL  - 118
ER  -
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