In his PhD thesis, Jonas Skogestad has delved into the underlying mechanisms of ventricular arrhythmias.


MAIN RESULTS:

  1. NKA activity is reduced in hypokalemia and Ankyrin B syndrome.
  2. Disruption of the ankyrin B/NKA/NCX domain could cause ventricular arrhythmias in Ankyrin B syndrome.
  3. Phosphodiesterase 2 inhibition increases NKA activity and prevents ventricular arrhythmias in heart failure and Ankyrin B syndrome.

THESIS DEFENCE:

Thesis: A search for novel treatments against ventricular arrhythmias
Candidate: Jonas Skogestad
Time: June 25, 2020 at 12:15
Place: Online-based solution, due to the covid-19 situation
Link to university website


SUMMARY:

(1) The activity of the ion pump Na+/K+-ATPase (NKA) is reduced in hypokalemia, increasing the susceptibility for cardiac arrhythmias. In rat cardiomyocytes exposed to hypokalemia, the NKA activity was reduced by 25%, mainly observed in the NKAα2 isoform, leading to increased intracellular Na+ and Ca2+-levels and higher frequency of spontaneous Ca2+-waves.

(3) Skogestad and co-workers showed increased sparks and waves of Ca2+ in cardiomyocytes following disruption of the interaction between NKA and the adaptor protein ankyrin B. Such disruption could be an important pathophysiological mechanism in the rare genetic disease Ankyrin B syndrome. The disruption abolished the correlation between NKA and Na+/Ca2+ exchanger (NCX) currents, increasing intracellular Na+-levels. None of these effects were seen when NKAα2 was inhibited.

(3) Na+ concentrations are higher near NKA than in the rest of the cytocol. Skogestad and co-workers conducted several experiments that suggested differential Na+ pools in the subsarcolemmal space. These findings could be important for cardiac contractility and genesis of cardiac arrhythmia.

(4) Inhibiting the cAMP-degrading enzyme phosphodiesterase 2 (PDE2) increases NKA activity and reverses the increased susceptibility of ventricular arrhythmias in mice models of heart failure and Ankyrin B syndrome.


REFERENCES:

(1) Aronsen, J. M., Skogestad, J., Lewalle, A., Louch, W. E., Hougen, K., Stokke, M. K., Swift, F., Niederer, S., Smith, N. P., Sejersted, O. M., & Sjaastad, I. (2015). Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+, K+‐ATPase α2 activity. The Journal of physiology593(6), 1509-1521.

(2) Skogestad, J., Lines, G. T., Louch, W. E., Sejersted, O. M., Sjaastad, I., & Aronsen, J. M. (2019). Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytesAmerican Journal of Physiology-Heart and Circulatory Physiology316(5), H941-H957.

(3) Skogestad, J., Aronsen, J. M., Tovsrud, N., Wanichawan, P., Hougen, K., Stokke, M. K., arlson, C. R., Sjaastad, I., Sejersted, O. M., & Swift, F. (2020). Coupling of the Na+/K+-ATPase to Ankyrin B controls Na+/Ca2+ exchanger activity in cardiomyocytes. Cardiovascular Research116(1), 78-90.

Latest News

October 05, 2024

Annual Symposium 2024: Winners and photos

More than 100 participants attended the 22nd Annual Norwegian Symposium on Heart Research, hosted by…

Read more
May 28, 2024

Photos from the workshop on Advancing Ischemic Heart Disease Research

Approximately 25 researchers met in Trondheim for the new workshop called “Advancing Ischemic Heart Disease…

Read more
May 14, 2024

Photos from Course in Cardiac Mechanics 2024

Cardiac researchers and clinical cardiologists need to know key concepts and terms for measuring and describing…

Read more
April 28, 2024

Professor Kristina H. Haugaa receives the 2024 Heart Research Award

The Norwegian Health Association has awarded the prestigious 2024 Heart Research Award (Hjerteforskningsprisen) to professor Kristina…

Read more
Norheart uses cookies for analytical purposes, content and ads customisation, and to further develop our services.
Accept
Learn more
Show again