Relative expression of immunolocalized connexins 40 and 43 correlates with human atrial conduction properties

Abstract

In human right atrium, conduction velocity is inversely related to immunodetectable Cx40 levels. The relative level of connexins 40 and 43 signal is strongly associated with atrial conduction properties, suggesting that interactions between the two connexins may result in novel coupling properties.

Relative Contributions of Connexins 40 and 43 to Atrial Impulse Propagation in Synthetic Strands of Neonatal and Fetal Murine Cardiomyocytes

“…14,16,17 Controversial reports have also been published about Cx40 remodeling, expression being upregulated in chronic human AF 16,18 or downregulated in a heterogeneous pattern in goats and humans. 14,17,19,20 Kanagaratnam et al 21 showed a strong correlation of electrical propagation velocity with the ratio of Cx43 (or Cx40) to total Cx immunosignal ([Cx43ϩCx40]). Thus, Cx43/[Cx43ϩCx40] was directly and Cx40/[Cx43ϩCx40] inversely related to propagation veloc-ity.…”

Is there a role for remodeled connexins in AF? No simple answers

“…Heteromeric means that a single connexon may be composed of different connexins such as Cx40 and Cx43 in atria, and coupled to another connexon comprised of different connexins. Cx40 and Cx43 colocalize in intercalated disks between atrial myocytes [48,54]. These two proteins have been demonstrated to interact in the formation of heteromeric/heterotypic gap junction channels in vitro [55,56].…”

“…Such remodeling might be the result of fibrosis that disrupts normal gap junction connections. Although fibrosis has not been found to be associated with all pathological causes of atrial fibrillation [48], fibrosis on a microscale might not always be recognized with standard histological techniques. It invariably occurs with aging in the form of fine longitudinally oriented collagenous microsepta [59].…”

“…Cx40 is expressed in high levels, 2 to 3 fold higher in the right atrium than the left [46]. It has been shown that the normal Cx40 distribution may also be heterogeneous with areas containing large amounts of Cx40 adjacent to others containing minimal or no Cx40 although hetrogeneities have not been precisely quantified [47][48][49]. The variable expression is likely to lead to inaccuracies in quantification of Cx40 in studies on remodeling in AF since only small samples of right atrial myocardium have been analyzed in most studies.…”

The Remodeling of Connexins Localized at Pulmonary Vein – Left Atria in Triggering and Maintenance of Atrial Fibrillation

“…What is more, the autonomic nervous system has a crucial role in the genesis, maintenance and abruption of atrial fibrillation (Duffy& Wit, 2008;Sandres et al,2004), and there is a fat pad localized in superior vena cava and the root of aorta as the origin of cardiac nerve, being called SVC-Ao fat pad (Kapa et al,2010;Volders ,2010;Ji et al,2010). The mechanism of atrial fibrillation involves multiple effects (Chiou et al,1997;Tsuboi et al,2000;Hoffmann et al, 2006;Haissaguerre et al1998;Wit & Boyden,2007), the expression of connexins is changed and is associated with increased propensity for arrhythmias (Kanagaratnam et al, 2002, Herve et al, 2007, Stergiopoulos et al, 1999, Verheule S et al, 2002, Kanagaratnam et al, 2007Valiunas et al,2001;Cottrell et al,2002;Elenes et al,1999). Pulmonary veins and left atria are the primary structure of genesis, persistence of atrial fibrillation.…”