Skip to main content

Normal and abnormal cardiac excitation: generation, propagation, and coupling to contraction

Objective

Cardiac arrhythmia is a major cause of morbidity and mortality in Europe and of growing socio-economic concern. Recent data suggest that novel mechanisms such as HCN channels, mechanical effects on Ca handling and ion flux balances, and cellular heterogeneity may trigger and/or permit the sustenance of arrhythmias. The novelty of our approach is to focus on these potentially crucial, but ill-investigated, mechanisms by uniting 8 leading labs from 5EU countries who focus on individual arrhythmogenic aspects, in a bid to combine their expertise and shed light on how physiological or compensatory mechanisms may turn arrhythmogenic, and how this may be controlled or corrected.

Prime targets are structured along three levels of functional integration:
-Membrane level: Role of HCN channels in the generation of normal and abnormal rhythm
-Cellular level: Role of electro-mechanical interaction in modulating contractile activity and electrophysiology
-Multicellular level: Role of heterogeneity in normal and remodelled tissue on electrical excitation and conduction

Scientific and technological objectives:
-To develop suitable experimental tools, including HCN transgenic mice, novel bradycardic and antiarrhythmic agents, control of mechano-electrical interactions, and the symbiosis of the above
-To acquire new knowledge on molecular mechanisms and pathways controlling generation and spread of excitation in normal and diseased cardiac tissue
-To combine advanced engineering techniques for 'top-down' development of novel experimental tools with mathematical 'bottom-up' integration of data from the molecular level to fundamental and clinical relevance

Based on the combination of skills and techniques not currently available in any single lab worldwide, we will provide novel insight into novel arrhythmogenic mechanisms, quantify their interrelation, target preventive and therapeutic interventions to reduce the societal and economical impact of cardiac arrhythmia

Call for proposal

FP6-2004-LIFESCIHEALTH-5
See other projects for this call

Coordinator

UNIVERSITA DEGLI STUDI DI FIRENZE
Address
Piazza S Marco 4
Firenze
Italy

Participants (7)

LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN
Germany
Address
Geschwister-scholl-platz 1
München
TECHNISCHE UNIVERSITÄT DRESDEN
Germany
Address
Helmholtzstr. 10
Dresden
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
University Offices, Wellington Square
Oxford
THE UNIVERSITY OF MANCHESTER
United Kingdom
Address
Street Oxford Road
Manchester
UNIVERSITA DEGLI STUDI DI MILANO
Italy
Address
Via Festa Del Perdono 7
Milano
UNIVERSITEIT MAASTRICHT
Netherlands
Address
Universiteitssingel 50
Maastricht
UNIVERSITY OF SZEGED
Hungary
Address
Dugonics Ter 13
Szeged