Molecular composition and functional properties of f-channels in murine embryonic stem cell-derived pacemaker cells

Journal of Molecular and Cellular Cardiology
Andrea BarbutiDario DiFrancesco

Abstract

Mouse embryonic stem cells (mESCs) differentiate into all cardiac phenotypes, and thus represent an important potential source for cardiac regenerative therapies. Here we characterize the molecular composition and functional properties of "funny" (f-) channels in mESC-derived pacemaker cells. Following differentiation, a fraction of mESC-derived myocytes exhibited action potentials characterized by a slow diastolic depolarization and expressed the I(f) current. I(f) plays an important role in the pacemaking mechanism of these cells since ivabradine (3 microM), a specific f-channel inhibitor, inhibited I(f) by about 50% and slowed rate by about 25%. Analysis of I(f) kinetics revealed the presence of two populations of cells, one expressing a fast- and one a slow-activating I(f); the two components are present both at early and late stages of differentiation and had also distinct activation curves. Immunofluorescence analysis revealed that HCN1 and HCN4 are the only isoforms of the pacemaker channel expressed in these cells. Rhythmic cells responded to beta-adrenergic and muscarinic agonists: isoproterenol (1 microM) accelerated and acetylcholine (0.1 microM) slowed spontaneous rate by about 50 and 12%, respectively. The same ago...Continue Reading

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Citations

Jan 5, 2011·Cardiovascular Research·Stefan HerrmannAndreas Ludwig
Oct 20, 2009·Journal of Molecular and Cellular Cardiology·Andrea BarbutiDario DiFrancesco
Jul 14, 2009·Journal of Molecular and Cellular Cardiology·Mirko BaruscottiAnnalisa Bucchi
Apr 28, 2009·Journal of Molecular and Cellular Cardiology·Chiara BrioschiMirko Baruscotti
Jul 5, 2015·BMC Cell Biology·Anne Günther, Arnd Baumann
Apr 13, 2010·Journal of Molecular and Cellular Cardiology·Zhan GaoMark E Anderson
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·David WeisbrodBernard Attali
Jan 12, 2017·Scientific Reports·Stephanie WeißgraeberKay Hamacher
Feb 20, 2010·Circulation Research·Dario DiFrancesco
Mar 2, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Daniele AvitabileAndrea Barbuti
Feb 11, 2020·Frontiers in Physiology·Dario DiFrancesco
May 9, 2021·Journal of Molecular and Cellular Cardiology·P BenzoniA Barbuti
Aug 18, 2021·Progress in Biophysics and Molecular Biology·Patrizia BenzoniAnnalisa Bucchi

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