Cardic Sodium Channels In Desease

• Applicant: Privatdozent Dr. Sebastian Maier
• Subject Area: Cardiology, Angiology
• Term: from 2004 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5422998

Voltage-gated sodium channels are responsible for the initiation of action potentials in most excitable cells. They are composed of a pore forming a-subunit and auxiliary ßsubunits. Different a subunit isoforms have distinct patterns of development and localization in the nervous system, skeletal and cardiac muscle, and they have distinct pharmacological and functional properties. Four different ß-subunits, have been identified and they are known to modulate channel gating, interact with extracellular matrix and play a role as cell adhesion proteins as well as they influence cell surface architecture. We described the composition of sodium channels in the heart and showed that besides the principal cardiac ot-isoform, brain-type isoforms are also expressed and that the different isoforms have distinct localizations within the ventricular myocyte and the sino-atrial node. This grant proposal focuses on the functional roles of the different sodium channel subunits for cardiac contractility, rhythmogenesis and arrhythmogenesis in normal and diseased human heart. We will investigate the involvement of different sodium channel subunits in cardiac remodeling due to heart failure in coronary artery disease. We hypothesize that changes in sodium channel isoform expression will lead to sodium current alterations with a possible responsibility for cardiac arrhythmias. Results obtained within this grant will contribute to the better understanding of arrhythmias and myocardial remodeling in diseased human heart.

• DFG Programme: Research Grants