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.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
calcium/calcium-mediated signaling pathway   IMP 1579960 RGD 
calcium/calcium-mediated signaling pathway   ISOS100A1 (Homo sapiens)1579960; 1579960 RGD 
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)


Additional Information