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S100A1 Enhances the L-type Ca2+ Current in Embryonic Mouse and Neonatal Rat Ventricular Cardiomyocytes
- Source :
- Journal of Biological Chemistry. 280:36019-36028
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- 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, p0.001) 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.
- Subjects :
- Cardiac function curve
medicine.medical_specialty
Time Factors
Calcium Channels, L-Type
medicine.drug_class
Biology
Biochemistry
Rats, Sprague-Dawley
Mice
Cytosol
Internal medicine
Cyclic AMP
medicine
Extracellular
Animals
Myocytes, Cardiac
Protein kinase A
Molecular Biology
Cells, Cultured
Rhodamines
Muscles
Calcium-Binding Proteins
S100 Proteins
Embryogenesis
Cell Biology
Protein kinase inhibitor
Cyclic AMP-Dependent Protein Kinases
Embryonic stem cell
Endocytosis
In vitro
Rats
Electrophysiology
Kinetics
Protein Transport
Spectrometry, Fluorescence
Endocrinology
Calcium
Homeostasis
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 280
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....1185f20e811a1c113e7243611e1d6f0e