Regulation of atrial gap junction protein expression and function by noradrenalin, angiotensin and atrial fibrillation. Aspects of receptor crosstalk

点击翻译按钮获取中文摘要

Atrial fibrillation (AF) is a common problem in cardiology and cardiac surgery. The success rate of treatment decreases with duration of AF due to remodelling involving (among other factors) altered expression of gap junction channels formed by the connexins (Cx) Cx40 and Cx43 and Cx-redistribution within the cell (from cell poles to the lateral side), thereby changing the tissues biophysical properties which may enable multiple wavelets and perpetuate AF being now fixed on a structural basis. Cx-expression is influenced by angiotensin via AT1, which is up-regulated in AF. Since noradrenalin is enhanced in many cardiac diseases (e.g. AF associated with hemodynamic relevant mitral valve disease), the role of ¿- or ß-adrenoceptor stimulation on cardiac Cx expression should be investigated in absence and presence of angiotensin in cultured rat cardiomyocytes, in comparison to human tissue samples. First experiments show that chronic ß- and (-adrenoceptor stimulation both can up-regulate Cx43. The signal transduction pathways should be investigated including a possible shift of the ß2-adrenoceptor from Gs to Gi (because of chronic ß-AR-stimulation) and the resulting changes in MAPKactivation. Since angiotensin-II can alter the expression of cardiac adrenoceptors via TGFß1 combined stimulation (catecholamines + angiotensin-II) should also be investigated.