The small EF-hand Ca2+ binding protein S100A1 increases contractility and Ca2+ cycling in rat cardiac myocytes.
S100A1 is an interesting Ca2+ binding protein with respect to muscle physiology as it is preferentially expressed in cardiac muscle and colocalizes with the sarcolemmal and the sarcoplasmic reticulum membranes as well as with the sarcomere. It is therefore conceivable that S100A1 may play a specific role in the regulation of cardiac Ca2+ homeostasis and contractility. We therefore investigated the impact of adenoviral S100A1 overexpression on fractional shortening (FS%) and systolic Ca2+ transients in adult rat cardiomyocytes as well as of S100A1 protein on SERCA activity in skinned cell preparation. In our setting S100A1 gene transfer increased FS% by 55%, systolic Ca2+ amplitudes by 62%, while S100A1 protein increased SERCA activity by 28%. Importantly, the gain in systolic Ca2+ supply was not only seen on basal conditions but also with isoproterenol-stimulated Ca2+ cycling. Thus, S100A1 enhances cardiac contractility by increasing intracellular Ca2+ fluxes at least in part due to a modulation of SERCA. Since earlier observations demonstrated S100A1 protein levels to be increased in compensatory hypertrophy and significantly downregulated in end stage heart failure, these functional data suggest that S100A1 is a novel determinant of cardiac function whose expression levels are causally related to the prevailing contractile state of the heart.
Remppis
Andrew
A
andrew.remppis@med.uni-heidelberg.de
Most
Patrick
P
Löffler
Eva
E
Ehlermann
Philipp
P
Bernotat
Juliane
J
Pleger
Sven
S
Börries
Melanie
M
Reppel
Michael
M
Fischer
Joachim
J
Koch
Walter J
WJ
Smith
Godfrey
G
Katus
Hugo A
HA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D005822:Genetic Vectors; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D009418:S100 Proteins; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014162:Transfection
D002135:Calcium-Binding Proteins; D009418:S100 Proteins; C110294:S100A1 protein; D002118:Calcium