Claudio Vinegoni, Ph.D. | Macrophages Facilitate Electrical Conduction in the Heart

Cell
Macrophages Facilitate Electrical Conduction in the Heart

Hulsmans, M., Clauss, S., Xiao, L., Aguirre, A. D., King, K. R., Hanley, A., Hucker, W. J., Wulfers, E. M., Seemann, G., Courties, G., Iwamoto, Y., Sun, Y., Savol, A. J., Sager, H. B., Lavine, K. J., Fishbein, G. A., Capen, D. E., Da Silva, N., Miquerol, L., Wakimoto, H., Seidman, C. E., Seidman, J. G., Sadreyev, R. I., Naxerova, K., Mitchell, R. N., Brown, D., Libby, P., Weissleder, R., Swirski, F. K., Kohl, P., Vinegoni, C., Milan, D. J., Ellinor, P. T., and Nahrendorf^#, M.

Cell 2017

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Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11b(DTR) mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.
@article{2017-CELL, author= {Hulsmans, M. and Clauss, S. and Xiao, L. and Aguirre, A. D. and King, K. R. and Hanley, A. and Hucker, W. J. and Wulfers, E. M. and Seemann, G. and Courties, G. and Iwamoto, Y. and Sun, Y. and Savol, A. J. and Sager, H. B. and Lavine, K. J. and Fishbein, G. A. and Capen, D. E. and Da Silva, N. and Miquerol, L. and Wakimoto, H. and Seidman, C. E. and Seidman, J. G. and Sadreyev, R. I. and Naxerova, K. and Mitchell, R. N. and Brown, D. and Libby, P. and Weissleder, R. and Swirski, F. K. and Kohl, P. and Vinegoni, C. and Milan, D. J. and Ellinor, P. T. and Nahrendorf<sup>#</sup>, M.}, title= {Macrophages Facilitate Electrical Conduction in the Heart}, journal= {Cell}, alternatejournal = {Cell}, year = {2017}, volume = {169}, number = {3}, pages = {510-+}, issn = {0092-8674}, doi = {10.1016/j.cell.2017.03.050}, pmcid = {PMC5474950}, pmid= {28431249} }
28431249

PMC5474950

10.1016/j.cell.2017.03.050

Abstract

"Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11b(DTR) mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction."

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For attribution in academic contexts, please cite this work as:

Hulsmans, M., Clauss, S., Xiao, L., Aguirre, A. D., King, K. R., Hanley, A., Hucker, W. J., Wulfers, E. M., Seemann, G., Courties, G., Iwamoto, Y., Sun, Y., Savol, A. J., Sager, H. B., Lavine, K. J., Fishbein, G. A., Capen, D. E., Da Silva, N., Miquerol, L., … Nahrendorf^#, M. (2017). Macrophages Facilitate Electrical Conduction in the Heart. Cell, 169(3), 510-+. https://doi.org/10.1016/j.cell.2017.03.050