Premium
Ca 2+ shuttling between endoplasmic reticulum and mitochondria underlying ouabain‐triggered Ca 2+ oscillations (1097.10)
Author(s) -
Fontana Jacopo,
Kruusmägi Markus,
Brismar Hjalmar,
Aperia Anita
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1097.10
Subject(s) - endoplasmic reticulum , cytosol , ouabain , mitochondrion , microbiology and biotechnology , calcium , intracellular , calcium signaling , chemistry , biology , biochemistry , enzyme , organic chemistry , sodium
Our group has studied the origin of Ca2+ oscillations triggered by the cardiotonic steroid ouabain, a highly specific ligand of Na+‐K+‐ATPase. It has been shown that these low frequency oscillations protect the cells from apoptosis by activating the NF κB/p65 survival subunit and inhibiting the intrinsic mitochondrial apoptotic pathway by reversing an imbalance between the apoptotic factor Bax and the antiapoptotic factor Bcl‐xL. The aim of this study is to reveal the identity and role of the intracellular compartments that are involved in ouabain‐triggered Ca2+ oscillations. Studies were first performed on COS7 cells which expressed genetic Ca2+ indicators targeted to mitochondria and cytosol. Following application of low doses of ouabain, we found that each cytosolic calcium wave was followed by a delayed mitochondrial calcium transient. The recovery of Ca2+ to normal levels was slower in mitochondria compared to cytosol, while the initial rate of increase was found to be similar in both compartments. Next, using an endoplasmic reticulum (ER)‐targeted genetic Ca2+ indicator, we observed rhythmic and simultaneous Ca2+ transients in both mitochondria and ER after ouabain application. We propose that Ca2+ shuttling between the ER and mitochondria may have a pivotal role in the propagation of ouabain triggered slow Ca2+ oscillations. Grant Funding Source : Swedish Research Council, Family Erling‐Persson Foundation, Märta and Gunnar V Philipson