Taxol stabilizes gap junctions and reduces ischemic ventricular arrhythmias in rats in vivo

Wang,Deguo; Xing,Wen; Wang,Xin; Zhu,Hongjun

doi:10.3892/mmr.2014.3137

Taxol stabilizes gap junctions and reduces ischemic ventricular arrhythmias in rats in vivo

Authors:
- Deguo Wang
- Wen Xing
- Xin Wang
- Hongjun Zhu
View Affiliations

Affiliations: Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Cardiology, Anhui Provincial Hospital, Hefei, Anhui 231000, P.R. China
Published online on: December 24, 2014 https://doi.org/10.3892/mmr.2014.3137
Pages: 3243-3248

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Kieken F, Mutsaers N, Dolmatova E, et al: Structural and molecular mechanisms of gap junction remodeling in epicardial border zone myocytes following myocardial infarction. Circ Res. 104:1103–1112. 2009. View Article : Google Scholar : PubMed/NCBI
2	Shaw RM, Fay AJ, Puthenveedu MA, von Zastrow M, Jan YN and Jan LY: Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell. 128:547–560. 2007. View Article : Google Scholar : PubMed/NCBI
3	Smyth JW, Hong TT, Gao D, et al: Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. J Clin Invest. 120:266–279. 2010. View Article : Google Scholar :
4	Vandroux D, Schaeffer C, Tissier C, et al: Microtubule alteration is an early cellular reaction to the metabolic challenge in ischemic cardiomyocytes. Mol Cell Biochem. 258:99–108. 2004. View Article : Google Scholar : PubMed/NCBI
5	Devillard L, Vandroux D, Tissier C, et al: Involvement of microtubules in the tolerance of cardiomyocytes to cold ischemia-reperfusion. Mol Cell Biochem. 307:149–157. 2008. View Article : Google Scholar
6	Teng M, Dang YM, Zhang JP, et al: Microtubular stability affects cardiomyocyte glycolysis by HIF-1alpha expression and endonuclear aggregation during early stages of hypoxia. Am J Physiol Heart Circ Physiol. 298:H1919–H1931. 2010. View Article : Google Scholar : PubMed/NCBI
7	Howarth FC, Calaghan SC, Boyett MR and White E: Effect of the microtubule polymerizing agent taxol on contraction, Ca²⁺ transient and L-type Ca²⁺ current in rat ventricular myocytes. J Physiol. 516(Pt 2): 409–419. 1999. View Article : Google Scholar
8	Xiao J, Zhao H, Liang D, et al: Taxol, a microtubule stabilizer, improves cardiac contractile function during ischemia in vitro. Pharmacology. 85:301–310. 2010. View Article : Google Scholar : PubMed/NCBI
9	Xiao J, Cao H, Liang D, et al: Taxol, a microtubule stabilizer, prevents ischemic ventricular arrhythmias in rats. J Cell Mol Med. 15:1166–1176. 2011. View Article : Google Scholar
10	Franz MR: Current status of monophasic action potential recording: theories, measurements and interpretations. Cardiovasc Res. 41:25–40. 1999. View Article : Google Scholar : PubMed/NCBI
11	Walker MJ, Curtis MJ, Hearse DJ, et al: The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion. Cardiovasc Res. 22:447–455. 1988. View Article : Google Scholar : PubMed/NCBI
12	Kawakami K, Chiba T, Katagiri N, et al: Paclitaxel increases high voltage-dependent calcium channel current in dorsal root ganglion neurons of the rat. J Pharmacol Sci. 120:187–195. 2012. View Article : Google Scholar : PubMed/NCBI
13	De Vuyst E, Boengler K, Antoons G, Sipido KR, Schulz R and Leybaert L: Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 163:469–483. 2011. View Article : Google Scholar : PubMed/NCBI
14	Calaghan SC, Le Guennec JY and White E: Cytoskeletal modulation of electrical and mechanical activity in cardiac myocytes. Prog Biophys Mol Biol. 84:29–59. 2004. View Article : Google Scholar
15	Tsuburaya R, Yasuda S, Ito Y, et al: Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs. J Mol Cell Cardiol. 51:329–336. 2011. View Article : Google Scholar : PubMed/NCBI
16	Chen Y, Zhang Q, Liao YH, et al: Effect of tumor necrosis factor-alpha on neutralization of ventricular fibrillation in rats with acute myocardial infarction. Mediators Inflamm. 2011:5652382011. View Article : Google Scholar
17	Guo X, Gao X, Wang Y, Peng L, Zhu Y and Wang S: IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion in rabbits by preserving the repolarization reserve. PLoS One. 7:e315452012. View Article : Google Scholar : PubMed/NCBI
18	Hori M, Sato H, Kitakaze M, et al: Beta-adrenergic stimulation disassembles microtubules in neonatal rat cultured cardiomyocytes through intracellular Ca²⁺ overload. Circ Res. 75:324–334. 1994. View Article : Google Scholar : PubMed/NCBI
19	Saetersdal T, Greve G and Dalen H: Associations between beta-tubulin and mitochondria in adult isolated heart myocytes as shown by immunofluorescence and immunoelectron microscopy. Histochemistry. 95:1–10. 1990. View Article : Google Scholar : PubMed/NCBI
20	Devillard L, Vandroux D, Tissier C, et al: Tubulin ligands suggest a microtubule-NADPH oxidase relationship in postischemic cardiomyocytes. Eur J Pharmacol. 548:64–73. 2006. View Article : Google Scholar : PubMed/NCBI
21	Beardslee MA, Lerner DL, Tadros PN, et al: Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia. Circ Res. 87:656–662. 2000. View Article : Google Scholar : PubMed/NCBI
22	Smyth JW, Hong TT, Gao D, et al: Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. J Clin Invest. 120:266–279. 2010. View Article : Google Scholar :