Anti-arrhythmic potential of novel polyunsaturated fatty acid analogues
Navn på bevillingshaver
Mark Skarsfeldt
Beløb
DKK 350,000
År
2018
Bevillingstype
Internationalisation Fellowships
Hvad?
Anti-arrhythmic potential of novel polyunsaturated fatty acid analogues. The electrical signals of the heart are governed by a balanced and synchronised flow of ions, in and out of the cardiac cell membrane via specialised cell membrane proteins, known as ion channels. Disturbances of the ionic currents underlying the cardiac action potential may cause lethal cardiac arrhythmias. The cardiac excitability is modulated by many substances and especially dietary fatty acids affect the repolarising currents of the cardiac action potential, which potentially can be anti-arrhythmic. I aim to develop novel polyunsaturated fatty acids (PUFAs) with anti-arrhythmic actions and determine their underlying molecular mechanism on the repolarising current in the heart.
Hvorfor?
The potential outcome of this project will benefit our understanding of how activation of the IKs current with PUFA analogues can reverse LQTS caused by genetic loss-of-function mutations. This knowledge will hopefully aid the understanding of the mechanisms and actions of PUFAs on the cardiac IKs channel. Furthermore, it could become a framework for development of novel IKs channel activators for treatment of LQTS, a highly unmet clinical need.
Hvordan?
Together with leading scientists from the University of Linköping, Sweden and University of Miami,USA, they have in great details investigated how dietary and specific synthetic PUFAs modulate the activity of the IKs channel. The molecular and mechanistic competence of the hosting labs in combination with animal model competence of the candidate will allow us to move towards more sophisticated experimental models for evaluating novel PUFA analogues.