Sequential changes in calcium transients during M phase regulate cardiomyocyte proliferation
Year: 2026
Type: article
Abstract: Heart muscle growth and regeneration require the proliferation of cardiomyocytes. Rapid pulsatile increases in cytosolic Ca2+ concentration, called calcium transients (CaTs), trigger cardiomyocyte contractions, but how cardiomyocytes adapt Ca2+ signaling during proliferation is largely unknown. Here, we show that cardiomyocyte proliferation requires changes in Ca2+ signaling. Cardiomyocytes undergo a sequence of CaT changes during M phase: CaT amplitudes begin to decline in prometaphase, reach a minimum in metaphase, rise during anaphase, and return to the original state in daughter cardiomyocytes. Spindle poles show decreased Ca2+ levels during prometaphase and metaphase. Localized reduction of Ca2+ levels at spindle poles is mediated by dynein 1-dependent SERCA2a accumulation. Active cyclin-dependent kinase 1 (CDK1) induces both the decrease in CaT amplitudes and the accumulation of SERCA2a at the spindle poles, whereas CDK1 inhibition reverses these effects. Forcing an increase in cytosolic Ca2+ levels by blocking SERCA2a during prometaphase and metaphase disrupts mitosis and produces binucleated cardiomyocytes, underscoring the essential role of Ca2+ signaling changes for cardiomyocyte proliferation.
Source: The Journal of Cell Biology
Institutions: Cornell University, Weill Cornell Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Richard King Mellon Foundation, University at Buffalo, State University of New York, Max Delbrück Center, German Centre for Cardiovascular Research, Charité – Universitätsmedizin Berlin, New York State College of Veterinary Medicine, University of Utah, McGowan Institute for Regenerative Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1006935754, Quantification of the decline of heart muscle cell proliferation and its reversal in pediatric patients, Genetic Resource for Optical Signaling, Photoreceptor Ciliopathies: UNC119 Paralogs and NPHP10/NPHP5, Lamin B2 regulates nuclear remodeling in cardiomyocyte terminal differentiation, G5012944769, Eliciting Heart Regeneration through Cardiomyocyte Division, G8522611149, G9000264003, Mechanistic clinical trial of Beta-blocker administration for reactivating cardiomyocyte division in Tetralogy of Fallot, University of Utah Core Vision Research Grant
OpenAlex ID: W7165851467