RGD Reference Report - S100A1 enhances the L-type Ca2+ current in embryonic mouse and neonatal rat ventricular cardiomyocytes. - Rat Genome Database

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S100A1 enhances the L-type Ca2+ current in embryonic mouse and neonatal rat ventricular cardiomyocytes.

Authors: Reppel, M  Sasse, P  Piekorz, R  Tang, M  Roell, W  Duan, Y  Kletke, A  Hescheler, J  Nurnberg, B  Fleischmann, BK 
Citation: Reppel M, etal., J Biol Chem. 2005 Oct 28;280(43):36019-28. Epub 2005 Aug 28.
RGD ID: 1579960
Pubmed: PMID:16129693   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M504750200   (Journal Full-text)

S100A1 is an EF-hand type Ca2+-binding protein with a muscle-specific expression pattern. The highest S100A1 protein levels are found in cardiomyocytes, and it is expressed already at day 8 in the heart during embryonic development. Since S100A1 is known to be involved in the regulation of Ca2+ homeostasis, we tested whether extracellular S100A1 plays a role in regulating the L-type Ca2+ current (I(Ca)) in ventricular cardiomyocytes. Murine embryonic (day 16.5 postcoitum) ventricular cardiomyocytes were incubated with S100A1 (0.001-10 microM) for different time periods (20 min to 48 h). I(Ca) density was found to be significantly increased as early as 20 min (from -10.8 +/- 1 pA/pF, n = 18, to -22.9 +/- 1.4 pA/pF; +112.5 +/- 13%, n = 9, p < 0.001) after the addition of S100A1 (1 microM). S100A1 also enhanced I(Ca) current density in neonatal rat cardiomyocytes. Fluorescence and capacitance measurements evidenced a fast translocation of rhodamine-coupled S100A1 from the extracellular space into cardiomyocytes. S100A1 treatment did not affect cAMP levels. However, protein kinase inhibitor, a blocker of cAMP-dependent protein kinase A (PKA), abolished the S100A1-induced enhancement of I(Ca). Accordingly, measurements of PKA activity yielded a significant increase in S100A1-treated cardiomyocytes. In vitro reconstitution assays further demonstrated that S100A1 enhanced PKA activity. We conclude that the Ca2+-binding protein S100A1 augments transsarcolemmal Ca2+ influx via an increase of PKA activity in ventricular cardiomyocytes and hence represents an important regulator of cardiac function.



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Objects Annotated

Genes (Rattus norvegicus)
S100a1  (S100 calcium binding protein A1)

Genes (Mus musculus)
S100a1  (S100 calcium binding protein A1)

Genes (Homo sapiens)
S100A1  (S100 calcium binding protein A1)


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