ALTERED PATTERN OF CONNEXIN40 DISTRIBUTION IN PERSISTENT ATRIAL-FIBRILLATION IN THE GOAT

Cx40 Distribution in Goat Atrial Fibrillation. Introduction: Since alt ered expression of gap junction proteins (connexins) in diseased myoca rdial tissue may lead to abnormal electrical coupling between cardiomy ocytes and hence contribute to arrhythmogenesis, the expression of con nexin(Cx)40 and Cx43 was studied in atrial appendage from goats in sin us rhythm (SR) and persistent atrial fibrillation (AF). Methods and Re sults: Biopsies were taken from the left and right atrial appendages f rom goats in SR or after pacing-induced persistent AF. Analyses of Cx4 0 and Cx43 mRNA and protein levels, using quantitative (competitive) p olymerase chain reaction and western blotting, respectively, revealed no significant changes in the overall expression of Cx40 and Cx43 as a result of persistent AF. At the cellular level, immunohistochemistry and confocal laser scanning microscopy showed a homogeneous distributi on of either connexin in atrial sections taken during SR. After induct ion of AF, the distribution of Cx43 gap junctions was unchanged wherea s the Cx40 pattern showed marked inhomogeneities with small areas (0.1 5 to 0.6 mm in diameter, 25% of section surface area) of low-density C x40 located between larger areas of normal (unchanged) Cx40 density. A ctivation mapping (244 electrodes, spatial resolution 2.25 mm) of the right atrial wall did not reveal changes in atrial conduction velocity . Conclusion: Pacing-induced persistent AF in the goat gave rise to ch anges in the spatial organization of Cx40 gap junctions. Although the overall conduction velocity appeared not to have changed, microheterog eneities in conduction due to the local redistribution of Cx40 gap jun ctions might have contributed to the initiation and maintenance of AF.