Cardiac Ca and Na Transport, E-C Coupling and Electrophysiology

Cardiac Ca and Na transport, E-C coupling and electrophysiology are the subject of hundreds of Bers’ papers, dozens of reviews, and The Book on these topics (below). This is a foundational area and strength in our lab, including many dozens of seminal quantitative mechanistic papers on the regulation of integrated Ca fluxes involved in cardiac contraction and relaxation, Ca current, Na current, K currents, Na/Ca exchange, Na/K-ATPase, SR Ca-ATPase, ryanodine receptor, plasma membrane Ca-ATPase, mitochondrial Ca uptake-extrusion/energetics and myofilament Ca activation, GPCR signaling. This includes fundamental characterization of each of these systems but also integration to the cellular and heart level with respect to cardiac dysfunction and arrhythmogenesis in diseases (e.g., hypertrophy, heart failure, diabetes), and always with an eye toward clinical relevance.

 

1. Bers DM:  Excitation-Contraction Coupling and Cardiac Contractile Force.  (Single Author Book) 2nd ed., Kluwer/Springer, Netherlands.  427 pp., 2001.  >2,900 citations) 

2. Bers DM:  Cardiac excitation–contraction coupling, Nature 415:198-205, 2002 (>5,200 citations)

3   Despa S, Lingrel JB, Bers DM.  Na/K-ATPase a2-isoform preferentially modulates Ca transients and SR Ca2+ release in cardiac myocytes. Cardiovasc Res. 95:480-486, 2012.

4.   Despa S, Shui B, Bossuyt J, Lang D, Kotlikoff MI, Bers DM. Junctional cleft [Ca]i measurements using novel cleft-targeted Ca sensors. Circ Res.  115:339-347, 2014. Highlighted by an accompanying Editorial. 

5.   Yuen GK, Galice S, Bers D. Subcellular localization of Na/K-ATPase isoforms in ventricular myocytes. J Mol Cell Cardiol. 108:158-169, 2017.

6. Hegyi B, Pölönen R-P, Hellgren KT, Ko CY, Ginsburg KS, Bossuyt J, Mercola M, Bers DM. Cardiomyocyte Na and Ca mishandling drives vicious cycle involving CaMKII, ROS, and ryanodine receptors. Bas Res Cardiol. 116(1):58, 2021. doi: 10.1007/s00395-021-00900-9