Diabetes and Thyroid Hormones Affect Connexin-43 and PKC-[epsilon] Expression in Rat Heart Atria

We have examined the changes of intercellular electrical coupling protein connexin-43 (Cx43) and of PKC-[straight epsilon] in heart atria of diabetic rats and/or after the treatment with triiodothyronine (T3). Diabetes was induced in Wistar-Kyoto rats by streptozotocin (50 mg/kg, i.v.) and atria were examined after 5 (acute stage) and 10 (chronic stage) weeks. T^sub 3^ (10 µg/100 g/day) was applied via a gastric tube for the last 10 days prior to the end of the experiments to non-diabetic and to the half of diabetic rats. Expression and phosphorylated status of Cx43, as well as expression of PKC-[straight epsilon], were analyzed by Western blots using mouse monoclonal anti-Cx43 and rabbit polyclonal anti-PKC-[straight epsilon] antibodies. We found that the Cx43 expression was significantly increased after the treatment with T^sub 3^ and in the acute diabetes. Both in diabetes and after T^sub 3^ treatment the phosphorylation of Cx43 isoforms was markedly suppressed compared to the nondiabetic and T^sub 3^-untreated controls. Such a down-regulation was less pronounced in diabetic rats after the T^sub 3^-treatment. The expression of atrial PKC-e was increased in diabetic rats. This increase was suppressed after T^sub 3^ administration and the expression was decreased in T^sub 3^-treated non-diabetic rats. We suggest that the reduced Cx43 phosphorylation in diabetic and hyperthyroid rats can deteriorate a cell-to-cell coupling and consequently facilitate a development of atrial tachyarrhythmia in diabetic or hyperthyroid animals. [PUBLICATION ABSTRACT]