Taxol stabilizes gap junctions and reduces ischemic ventricular arrhythmias in rats in vivo
Deguo Wang1, Wen Xing1, Xin Wang1
1Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
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.
Insights
Taxol stabilizes microtubules, preserving connexin 43 (Cx43) expression and distribution. This stabilization reduces ventricular arrhythmias (VAs) during myocardial ischemia and reperfusion, offering a potential therapeutic strategy.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pharmacology
Background:
- Connexin 43 (Cx43) dynamics are microtubule-dependent.
- Cx43 dysfunction in ischemic myocardium links to ventricular arrhythmias (VAs).
Purpose of the Study:
- Investigate microtubule effects on Cx43 expression and distribution.
- Assess taxol's impact on VAs during myocardial ischemia-reperfusion.
Main Methods:
- Rat model of myocardial ischemia-reperfusion.
- Taxol administration at varying concentrations.
- Electrophysiological recordings (monophasic action potentials).
- Immunoblotting and immunofluorescence for tubulin and Cx43.
Main Results:
- Taxol pretreatment prevented microtubule depolymerization.
- Improved Cx43 expression and redistribution observed.
- Reduced incidence of VAs and improved action potential duration (APD) parameters.
- Taxol ameliorated APD shortening and dispersion.
Conclusions:
- Taxol mitigates ischemic VAs by stabilizing microtubules.
- Preservation of Cx43 is a key mechanism.
- Microtubule stabilization represents a potential therapeutic approach for ischemic heart conditions.


