title: Taxol stabilizes gap junctions and reduces ischemic ventricular arrhythmias in rats in vivo.
abstract: The dynamic movements of connexin 43 (Cx43) are regulated by microtubules and their associated proteins. Dysfunction of Cx43 in the ischemic myocardium is correlated with ventricular arrhythmias (VAs). The present study aimed to determine the effects of microtubules on Cx43 expression and distribution in myocardial tissue, as well as to examine the susceptibility of the heart to VAs during acute myocardial ischemia and reperfusion. Rats were subject to left coronary artery occlusion for 20 min followed by 20 min reperfusion and received taxol at different concentrations (0.1, 0.3 and 0.9 µmol·kg‑1 in 0.5 ml saline) intraperitoneally. Monophasic action potentials at the epicardium were recorded and analyzed using an electrocardiogram. Immunoblots and immunofluorescence staining were used to detect tubulin polymerization and Cx43 expression and distribution. Taxol pretreatment significantly ameliorated the depolymerization of microtubules, improved Cx43 expression and redistribution, reduced the occurrence of VAs, ameliorated shortening of 90% repolarization action potential durations (APD)90 and improved APD dispersion during myocardial ischemia‑reperfusion. The present study demonstrated that taxol reduced ischemic VAs and its mechanism may be correlated with the preservation of Cx43 by stabilizing microtubules.
authors.affiliation: Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Deguo
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Anhui Provincial Hospital, Hefei, Anhui 231000, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography; D017629:Gap Junctions / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D017202:Myocardial Ischemia / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D014404:Tubulin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018031:Connexin 43; D014404:Tubulin; D017239:Paclitaxel