title: Gap junction remodelling is involved in the susceptibility of diabetic rats to hypokalemia-induced ventricular fibrillation.
abstract: The objective of the present study was to examine the susceptibility of diabetic rats with cardiomyopathy to hypokalemia-induced ventricular fibrillation and to localize gap junction protein connexin-43 as well as subcellular changes that may be involved in the development of severe arrhythmia. Our results showed a significantly higher incidence of sustained ventricular fibrillation in diabetic hearts as compared with control hearts, 80% vs 20%, respectively. Diabetic cardiomyopathy itself was accompanied by a distinct decrease in connexin-43-immunopositive gap junctions. Moreover, interstitial fibrosis and subcellular alterations to various degrees were observed in diabetic hearts, and a further deterioration of the ultrastructure and impairment of intercellular junctions, and a stronger local decrease in connexin-43 levels due to hypokalemia were found. These changes were heterogeneously distributed throughout the myocardium and occurred earlier and were more pronounced in diabetic hearts than control hearts. In conclusion, our results indicate that diabetic cardiomyopathy is associated with down-regulation of gap junction proteins and may account for the higher vulnerability of diabetic rats to ventricular fibrillation in combination with impairment of intercellular communication due to hypokalemia.
authors.affiliation: Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. usrdokru@savba.sk
authors.forename: Ludmila
authors.initials: L
authors.lastname: Okruhlicova
authors.forename: Narcis
authors.initials: N
authors.lastname: Tribulova
authors.forename: Melania
authors.initials: M
authors.lastname: Misejkova
authors.forename: Marek
authors.initials: M
authors.lastname: Kucka
authors.forename: Radovan
authors.initials: R
authors.lastname: Stetka
authors.forename: Jan
authors.initials: J
authors.lastname: Slezak
authors.forename: Mordechai
authors.initials: M
authors.lastname: Manoach
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004562:Electrocardiography; D017629:Gap Junctions / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007008:Hypokalemia / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism*
chemical_list: D018031:Connexin 43