Abstract
Cardiac myocyte contraction depends on transmembrane L-type Ca2+ currents and the ensuing release of Ca2+ from the sarcoplasmic reticulum. Here we show that these L-type Ca2+ currents are essential for cardiac pump function in the mouse at developmental stages where the functional significance of the heart becomes imperative to blood flow and to the continuing growth and survival of the embryo. Disruption of the Cavβ2 gene, which encodes for the predominant ancillary β subunit of cardiac Ca2+ channels, resulted in diminished L-type Ca2+ currents in cardiomyocytes of embryonic day 9.5 (E9.5). This led to a functionally compromised heart, causing defective remodeling of intra- and extraembryonic blood vessel s and embryonic death following E10.5. The defects in vascular remodeling were also observed when the Cavβ2 gene was selectively targeted in cardiomyocytes, demonstrating that they are secondary to cardiac failure rather than a result of the lack of Cavβ2 proteins in the vasculature. Partial rescue of the Ca2+channel currents by a Ca2+channel agonist significantly postponed embryonic death in Cavβ2 −/−mice. Taken together, these data strongly support the essential role of L-type Ca2+ channel activity in cardiomyocytes for normal heart development and function and that this is a prerequisite for proper maturation of the vasculature.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Kaestner, L. (2013). Reduced Cardiac L-Type Ca2+ Current in Cavß -/-2 Embryos Impairs Cardiac Development and Contraction With Secondary Defects in Vascular Maturation. In: Calcium signalling. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-34617-0_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-34617-0_17
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-34616-3
Online ISBN: 978-3-642-34617-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)