Aims: 

Functional electrical and metabolic communication at the gap junction connexin channels ensures myocardial synchronisation, while connexin abnormalities are thought to be arrhythmogenic. We examined, therefore, topology, expression and phosphorylation of connexin-43 (C ( 43) as well as susceptibility of the heart to ventricular fibrillation (VF) in various models of cardiomyopathy.

Methods: 

Experiments were conducted on male adult spontaneously hypertensive rat, STZ-diabetic rat and hyperthyroid rat hearts. Distribution of C ( 43, its expression and phosphorylation were analysed using immunodetection and Western blotting with mouse MAb. Susceptibility to VF was examined in isolated heart preparation using electrical stimulation or hypokalemic perfusion.

Results: 

Immunodetection revealed besides end-to-end (intercalated disc-related) enhanced expression of side-to-side C ( 43 positive gap junctions in hypertensive and hyperthyroid rat hearts. In addition, total C ( 43 and its phosphorylated isoforms were significantly decreased in hyperthyroid and hypertensive, while increased in diabetic rat hearts. In correlation diabetic rats were less while hypertensive and hyperthyroid rats much more prone to develop VF. Interestingly, susceptibility to VF was increased in diabetic rats treated with thyroid hormone that was linked with suppression of C ( 43 expression and phosphorylation.

Conclusions: 

These findings indicate that intercellular channel protein C ( 43 is involved in the modulation of susceptibility of the heart to malignant arrhythmias. Abnormal distribution and down-regulation of C ( 43 increase a risk for VF.

Supported by APVV grants 51-059505 and 51-015905.