Abstract 18999: The Effects of the Connexin40 Mutations P88S and G38A on Cardiac Physiology in the Intact Animal
Introduction: Prior patch clamping studies have revealed that the somatic human connexin40 mutations P88S and G38A, identified within the atria of patients with atrial fibrillation (AF), are associated with reduced gap junction conductances when compared to wild type connexin40 (wtCX40). Our aim was to phenotype the rat heart following expression of these mutations by somatic gene transfer.
Methods: A mix of pluronic F127, trypsin, and 107 vector genomes of lentivirus was painted onto the left atrium of adult Sprague-Dawley rats via a left thoracotomy. Rats were randomised to receive lentivirus containing a transgene encoding either wtCX40, P88S, G38A or eGFP. Electrophysiology studies (EPS) consisting of surface and trans-oesophageal electrocardiograms (ECG) were performed under anaesthesia just prior to and 7 days after surgery. Following day 7 EPS, atria were excised, sectioned, and examined histologically with Sirius Red and Haematoxylin and Eosin. Data are expressed as means ± standard deviations.
Results: At day 7, eGFP expression revealed approximately 5% heterogeneous atrial transduction. Rats transduced to express either P88S or G38A possessed significantly longer mean P wave durations and AF when compared to eGFP controls as shown in the table. There were no significant differences in all other characteristics.
Conclusion: The human somatic connexin40 mutations P88S and G38A slow atrial conduction as evidenced by prolonged P wave durations at day 7. In addition, heterogonous expression of P88S and G38A within the atrial myocardium increases the propensity for inducible atrial fibrillation.
- © 2012 by American Heart Association, Inc.