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Published on: February 21, 2016
Sick sinus syndrome in HCN1-deficient mice
Stefanie Fenske1, Stefanie C Krause, Sami I H Hassan
1Center for Integrated Protein Science CIPS-M and Zentrum für Pharmaforschung, Department Pharmazie (S.F., S.C.K., S.I.H.H., E.B., F.A., R.B., V.H., C.P., M.B., C.A.W.-S.) and Medizinische Klinik und Poliklinik I, Klinikum Großhadern (C.K., P.L., T.Z.), Ludwig Maximilians University, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.K., P.L., T.Z., M.B., C.A.W.-S.); Max-Planck-Institut für Psychiatrie München, Germany (C.T.W.); and School of Physics & Astronomy, University of Manchester, UK (H.Z.).
The HCN1 protein is crucial for maintaining a stable heart rate. Mice lacking HCN1 exhibit congenital sinus node dysfunction (SND), offering a new model for studying this condition.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Genetics
Background:
- Sinus node dysfunction (SND) is a significant cause of sudden cardiac death, often linked to heart failure and hypertension.
- While acquired SND is well-studied, the molecular mechanisms of congenital SND remain largely unknown.
Purpose of the Study:
- To investigate the role of the HCN1 protein in the molecular and cellular mechanisms underlying congenital sinus node dysfunction.
- To characterize the cardiac phenotype of HCN1-deficient mice.
Main Methods:
- Functional characterization of sinoatrial node cells and explanted preparations from HCN1-deficient mice.
- In vivo telemetric electrocardiography, echocardiography, and electrophysiology studies in HCN1-deficient mice.
Main Results:
- HCN1 protein is highly expressed and colocalized with HCN4 in the sinoatrial node.
- HCN1-deficient mice display congenital SND, including bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, and sinus pauses.
- HCN1 deficiency leads to severely reduced cardiac output in mice.
Conclusions:
- HCN1 is essential for stabilizing the sinoatrial node's leading pacemaker region, ensuring stable heart rate and beat-to-beat variation.
- HCN1-deficient mice represent a valuable genetic model for human congenital sinus node dysfunction.
