抄録
In the myocardium, dysfunction of the gap junction impairs intercellular electrical coupling and can be one of arrhythmogenic factors. The function of the gap junction depends essentially on characteristics of the connexin which composes the gap junction channel. In this study, relation between changes of expression of the connexin43 (Cx43) and susceptibility of myocardium to fibrillation was examined on the aconitine (AC)-induced cardiac fibrillation model in the isolated hearts of adult guinea-pig and rat. In the normal hearts, ventricular flutter induced by AC (0.1μM) (on Langendorff perfusion) shifted spontaneously to fibrillation about 10 min later. Low concentration of heptanol shifted the flutter to the fibrillation within several seconds showing asynchronous intercellular electrical interactions. At the beginning of the fibrillation, expression of Cx43 at the intercalated disk (ID) was sporadic coupled with a reduction of PKA-mediated and an augmentation of PKCε-mediated phosphorylation of Cx43. These events were enhanced as the fibrillation was advanced. During fibrillation, level of cardiac tissue Angiotensin II (Ang.II) was raised. In Ang.II analog- or PMA-pretreated hearts and diabetic hearts in which PKCε was activated, expression of Cx43 at ID was sparse. In these pathological hearts, time of shift from the flutter to the fibrillation was remarkably shortened within 3 min. These results suggest that remodeling of Cx43 due to an activation of PKCε and an acceleration of proteolytic degradation makes the heart susceptible to the fibrillation. [Jpn J Physiol 55 Suppl:S91 (2005)]
