Intracellular Redistribution of Left Ventricular Connexin 43 Contributes to the Remodeling of Electrical Properties of the Heart in Insulin-resistant Elderly Rats


Journal of Histochemistry and Cytochemistry, vol.70, no.6, pp.447-462, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 70 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1369/00221554221101661
  • Journal Name: Journal of Histochemistry and Cytochemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.447-462
  • Keywords: aging, arrhythmia, connexin phosphorylation, EEG, electrical activity, heart function, insulin resistance, metabolic syndrome
  • Lokman Hekim University Affiliated: Yes


© The Author(s) 2022.The correlation between long-QT and connexin 43 (Cx43) status and localization in elderly rats was determined to demonstrate a correlation between insulin resistance (I-R), ischemia-reperfusion, aging, and heart dysfunction. Male Wistar rats are grouped as 24-month-old rats (Aged-group), those with metabolic syndrome (8 months old; MetS-group), or controls (8 months old; Con-group). Both experimental groups have long-QT and low heart rate. Immunohistochemical imaging and quantification showed marked decreases in Cx43 staining of intercalated disc with less localizations in the Aged-group and MetS-group. The lateralization of Cx43 on longitudinal cell membrane was significantly high in the MetS-group than in the Con-group with no significant change in the Aged-group. Its significant cytoplasmic internalization was higher in the Aged-group than in the MetS-group. There were marked decreases in phospho-Cx43 (pCx43) staining of intercalated disc with less localizations in both groups than in the Con-group. Furthermore, lateralization of pCx43 was significantly low in the Aged-group and MetS-group, whereas there were no significant changes in the cytoplasmic internalization of both groups compared with the Con-group. Furthermore, the ratio of pCx43 to Cx43 was significantly small in both groups. We determined increases in RhoA and endothelin-1 in both groups, further supporting decreases in pCx43. Our data indicate the important role of I-R on long-QT in aging heart through alterations in both Cx43 protein level and localizations, leading to an abnormal spreading of ventricular repolarization in I-R heart: