Advanced Light Microscopy facility – ALM
Karolinska Institutet and KTH Royal Institute of Technology
The main topic in our research is to understand the many functional aspects of Na,K-ATPase, the salt pump that is the major determinant of intracellular ion homeostasis and which has recently been shown to also function as a signal transducer.
Studies of Na,K –ATPase has become a hot topic, since a number of monogenetic diseases, associated with cognitive deficits, therapy resistant epilepsy and dystonia, have recently been found to be due to single mutations in the catalytic subunit of the neuronal isoform of Na,K-ATPase. We have made several pioneering contributions to the understanding of the specific function of neuronal Na,K-ATPase, by identification of its sub-cellular localization in the neuron with STED and PALM microscopy and by demonstrating its functional importance for recovery of intracellular sodium after high neuronal activity by developments of subcellular real time sodium imaging. Currently we are studying the functional consequences of disease mutations, using a variety of imaging and modelling approaches.
We have also pioneered the field of Na,K-ATPase signaling, describing how the endogenous cardiotonic steroid ouabain, which is a specific Na,K-ATPase ligand, triggers an oscillating calcium signal, where the downstream effects are activation of the anti-apoptotic factor Bcl-xL and protection from apoptosis. This signal has been shown to play a major role for protection against apoptosis in fetal malnourishment, in infections with shigatoxin producing E Coli and in chronic kidney disease and we are now seeking to identify the genes activated by the ouabain/Na,K-ATPase calcium signal.
Hjalmar Brismar, Professor
Anita Aperia, Senior Professor
Kristoffer Bernhem, PhD-student
Hans Blom, researcher
Ievgeniia Burlaka, PhD-student
Jacopo Fontana, Postdoc
Elin Forslund, PhD-student
Thomas Frisk, Research engineer
Nicolas Fritz, Postdoc
Karolin Guldevall, PhD-student
Eli Gunnarson, researcher
Nina Illarionova, PhD-student
Otto Manneberg, Research engineer
Linnéa Nilsson, PhD-student
Per Olofsson, PhD-student
Lena Scott, researcher
Lill-Britt Svensson, Laboratory engineer
Linda Westin, PhD-student
Björn Önfelt, Associate Professor
- Liebmann T, Blom H, Aperia A, Brismar H, “Nanoscale elucidation of Na,K-ATPase isoforms in dendritic spines”, Optical Nanoscopy 2013; 2:6
- Blom H, Rönnlund D, Scott L, Westin L, Widengren J, Aperia A, Brismar H, “Spatial distribution of DARPP-32 in Dendritic Spines”, PLoS ONE 2013; 8(9):e75155.
- Burlaka I, Liu XL, Rebetz J, Arvidsson I, Yang L, Brismar H, Karpman D, Aperia A. “Ouabain Protects against Shiga Toxin-Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL.” J Am Soc Nephrol. 2013 24(9):1413-23
- Azarias G, Kruusmagi M, Connor S, Akkuratov EE, Liu XL, Lyons D, Brismar H, Broberger C, Aperia A. “A specific and essential role for Na,K-ATPase α3 in neurons co-expressing α1 and α3” J. Biol. Chem. 2013;288(4):2734-43
- Li J, Khodus Gr, Kruusmägi M, Kamali-Zare P, Liu XL, Eklöf AC, Zelenin S, Brismar H, Aperia A. Ouabain protects against adverse developmental programming of the kidney. Nature Comm 2010; 1(4):1-7