Download Cardiac sodium channels in heart failure

Cardiac sodium channels in heart failure
Voltage-gated sodium channels are responsible for the initiation of
action potentials in most excitable cells. They are composed of a pore
forming α-subunit and auxiliary β-subunits. Different α-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 β-subunits
have been identified and 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 α-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 the diseased human heart.
Project leader:
Prof. Dr. S. Maier,
Dr. S. Kaufmann
Contact:
e-mails:
[email protected]
Participating scientists:
Dr. Jenny Muck
Dr. Marco Abesser