Store-Operated Calcium Entry Increases Nuclear Calcium in Adult Rat Atrial and Ventricular Cardiomyocytes
Store-operated calcium entry (SOCE) in cardiomyocytes may be involved in cardiac remodeling, but the underlying mechanisms remain elusive. We hypothesized that SOCE may increase nuclear calcium, which alters gene expression via calcium/calmodulin-dependent enzyme signaling, and elucidated the und...
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Ngā kaituhi matua: | , , |
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Hōputu: | Tuhinga |
Reo: | Ingarihi |
I whakaputaina: |
Philipps-Universität Marburg
2023
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Urunga tuihono: | Kuputuhi katoa PDF |
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Whakarāpopototanga: | Store-operated calcium entry (SOCE) in cardiomyocytes may be involved in cardiac remodeling,
but the underlying mechanisms remain elusive. We hypothesized that SOCE may increase
nuclear calcium, which alters gene expression via calcium/calmodulin-dependent enzyme signaling,
and elucidated the underlying cellular mechanisms. An experimental protocol was established
in isolated adult rat cardiomyocytes to elicit SOCE by re-addition of calcium following complete
depletion of sarcoplasmic reticulum (SR) calcium and to quantify SOCE in relation to the electrically
stimulated calcium transient (CaT) measured in the same cell before SR depletion. Using confocal
imaging, calcium changes were recorded simultaneously in the cytosol and in the nucleus of the cell.
In ventricular myocytes, SOCE was observed in the cytosol and nucleus amounting to �15% and
�25% of the respective CaT. There was a linear correlation between the SOCE-mediated calcium
increase in the cytosol and nucleus. Inhibitors of TRPC or Orai channels reduced SOCE by �33–67%,
whereas detubulation did not. In atrial myocytes, SOCE with similar characteristics was observed in
the cytosol and nucleus. However, the SOCE amplitudes in atrial myocytes were �two-fold larger
than in ventricular myocytes, and this was associated with �1.4- to 3.6-fold larger expression of
putative SOCE proteins (TRPC1, 3, 6, and STIM1) in atrial tissue. The results indicated that SOCE in
atrial and ventricular myocytes is able to cause robust calcium increases in the nucleus and that both
TRPC and Orai channels may contribute to SOCE in adult cardiomyocytes. |
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Whakaahutanga tūemi: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
DOI: | 10.3390/cells12232690 |