The natural pacemaker of the heart
Name of applicant
Alicia Lundby
Institution
University of Copenhagen
Amount
DKK 4,472,900
Year
2017
Type of grant
Semper Ardens: Accelerate
What?
The rhythmic contraction of our heart is controlled by electrical impulses that travel throughout the cardiac muscle. The signal is generated by the sinus node, which can be thought of as the natural pacemaker of our heart. The question is, what it is that makes the sinus node unique, enabling it to generate a repetitive firing of electrical signals thereby ensuring the foundation for the rhythmic cardiac contraction? We aim to perform an in-depth investigation of the molecular composition of the cardiac sinus node to explain the molecular interplay that endows this particular tissue with a unique ability to generate continuous rhythmic cardiac contractions. Furthermore, the role of the sinus node in a common cardiac disease, heart failure, shall be investigated.
Why?
The research's outcome will contribute to clarification of the molecular players underlying the rhythmic contraction of our heart, and hence form a foundation for addressing protein dysfunctionalities in sinus node pathologies and rhythm disorders.
How?
We will characterise the unique protein expression landscape of the natural cardiac pacemaker through execution of high-resolution mass spectrometry based cardiac proteomics experiments. Sinus node and abutting atrial tissue biopsies will be collected from mice, either with healthy or failing hearts. Extracted proteins are measured by high-resolution mass spectrometry to achieve the most comprehensive cardiac proteomes that are technologically possible today. Global protein expression profiles will be analysed to identify key protein differences between sinus node and atrial biopsies, and Markov-models will be applied to evaluate findings involved in membrane voltage oscillations. Our cardiac proteomics endeavors will enable unbiased investigations of essentially all sinus node proteins.