Signalling pathways activated by atrial dilatation and their relationship to atrial fibrillation

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Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and its immediate precursor phosphatidylinositol(4,5)bisphosphate (PIP2) in atrial fibrillation with a view to providing targets for therapy that are well tolerated. There is recent evidence that Ins(1,4,5)P3 and PIP2 can contribute to atrial fibrillation. Over the next 3 years we will study cellular signalling responses to acute and chronic dilatation of the atria and examine the relationship of these findings to clinical atrial fibrillation. We will identify the G protein and phospholipase C subtypes involved in responses to stretch and use tools developed in these studies in experiments with atrial fibrillation models.