Abstract
Mechanosensitive channels have been determined to work as transducers of mechanoelectric feedback in the heart, which is associated with the generation of arrhythmias. Recent studies have investigated the role of the cytoskeleton in ion channels control. This study explored the ability of taxol to inhibit stretch-induced electrophysiological alterations in the ischemic myocardium. Thirty-two Wistar rats were randomly divided into four groups: normal control group (n=9), taxol group (n=7), myocardial infarction (MI) group (n=9), and MI+taxol group (n=7). After Langendorff perfusion, the isolated hearts were stretched for 5 s by balloon inflation to 0.2 or 0.3 mL. The effects of stretching on 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVB), and ventricular tachycardia (VT) were observed for 30 s. Stretching increased MAPD90 in both the normal control and MI groups, but MAPD90 increased more in the MI group for the same degree of stretch. Taxol (5 μmol L−1) had no effect on MAPD90 under baseline, unstretched conditions, but MAPD90 in the taxol group was slightly increased after stretching compared with the normal control group (P>0.05). However, taxol reduced MAPD90 in infarcted myocardium (P<0.05 at ΔV=0.3 mL). The incidences of PVB and VT in the MI group were higher than in the normal control group (both P<0.01). Taxol had no effect on the occurrence of arrhythmias in normal myocardium, but it inhibited PVB and VT in infarcted hearts (both P<0.01). Thus changes in MAPD and the occurrence of arrhythmias caused by mechanical stretching of the myocardium could be inhibited by taxol in isolated rat hearts during AMI, indicating the involvement of tubulin in mechanoelectric feedback in AMI.
Similar content being viewed by others
References
Husic M, Norager B, Egstrup K, et al. Usefulness of left ventricular diastolic wall motion abnormality as an early predictor of left ventricular dilation after a first acute myocardial infarction. Am J Cardiol, 2005, 96: 1186–1189, 10.1016/j.amjcard.2005.06.053, 16253579
Thygesen K, Uretsky B F. Acute ischaemia as a trigger of sudden cardiac death. Eur Heart J Suppl, 2004, 6: D88–D90, 10.1016/j.ehjsup.2004.05.006
Lab M J. Mechanosensitive-mediated interaction, integration, and cardiac control. Ann N Y Acad Sci, 2006, 1080: 282–300, 1:CAS:528:DC%2BD2sXmtlyntg%3D%3D, 10.1196/annals.1380.022, 17132790
Garan A R, Maron B J, Wang P J, et al. Role of streptomycin-sensitive stretch-activated channel in chest wall impact induced sudden death (commotio cordis). J Cardiovasc Electrophysiol, 2005, 16: 433–438, 10.1046/j.1540-8167.2005.40664.x, 15828890
Janmey P A. The cytoskeleton and cell signaling: component localization and mechanical coupling. Physiol Rev, 1998, 78: 763–781, 1:CAS:528:DyaK1cXltFGmtrY%3D, 9674694
Johnson B D. The company they keep: ion channels and their intracellular regulatory partners. Adv Second Messenger Phosphoprotein Res, 1999, 33: 203–228, 1:STN:280:DyaK1M3jsVOnsQ%3D%3D, 10218120
Perozo E, Cortes D M, Sompornpisut P, et al. Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature, 2002, 418: 942–948, 1:CAS:528:DC%2BD38XmsFWksbc%3D, 10.1038/nature00992, 12198539
Morris C E. Mechanoprotection of the plasma membrane in neurons and other non-erythroid cells by the spectrin-based membrane skeleton. Cell Mol Biol Lett, 2001, 6: 703–720, 1:CAS:528:DC%2BD3MXoslamurw%3D, 11598643
Maingret F, Fosset M, Lesage F, et al. TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem, 1999, 274: 1381–1387, 1:CAS:528:DyaK1MXpsFOjsA%3D%3D, 10.1074/jbc.274.3.1381, 9880510
Shen M R, Chou C Y, Hsu K F, et al. Modulation of volume-sensitive Cl-channels and cell volume by actin filaments and microtubules in human cervical cancer HT-3 cells. Acta Physiol Scand, 1999, 167: 215–225, 1:CAS:528:DC%2BD3cXhslWksA%3D%3D, 10.1046/j.1365-201x.1999.00611.x, 10606823
Hein S, Scheffold T, Schaper J. Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium. J Thorac Cardiovasc Surg, 1995, 110: 89–98, 1:STN:280:DyaK2MzjtlymsA%3D%3D, 10.1016/S0022-5223(05)80013-3, 7609573
Iwai K, Hori M, Kitabatake A, et al. Disruption of microtubules as an early sign of irreversible ischemic injury: immunohistochemical study of in situ canine hearts. Circ Res, 1990, 67: 694–706, 1:STN:280:DyaK3cznsVCktw%3D%3D, 1697795
Armstrong S C, Ganote C E. Flow Cytometric analysis of isolated adult cardiomyocytes: vinculin and tubulin fluorescence during metabolic inhibition and ischemia. J Mol Cell Cardiol, 1992, 24: 149–162, 1:CAS:528:DyaK38XisFehu7Y%3D, 10.1016/0022-2828(92)93151-9, 1583698
Dick D J, Lab M J. Mechanical modulation of stretch-induced premature ventricular beats: induction of mechanoelectric adaptation period. Cardiovasc Res, 1998, 38: 181–191, 1:CAS:528:DyaK1cXjvVSjtbw%3D, 10.1016/S0008-6363(97)00314-3, 9683920
Walker M J, Curtis M J, Hearse D J, et al. The Lambeth Conventions: guidelines for the study of arrhythmias in ischemia infarction, and reperfusion. Cardiovasc Res, 1988, 22: 447–455, 1:STN:280:DyaL1Mzgtl2kug%3D%3D, 10.1093/cvr/22.7.447, 3252968
Nilius B, Boldt W. Stretching-induced changes in the action potential of the atrial myocardium. Acta Biol Med Ger, 1980, 39: 255–264, 1:CAS:528:DyaL3cXlsVOgtbY%3D, 7424344
Chen R L, Penny D J, Greve G, et al. Stretch-induced regional mechanoelectric dispersion and arrhythmia in the right ventricle of anesthetized lambs. Am J Physiol Heart Circ Physiol, 2004, 286: H1008–H1014, 1:CAS:528:DC%2BD2cXitlShsLk%3D, 10.1152/ajpheart.00724.2003, 14766676
Isenberg G, Kazanski V, Kondratev D, et al. Differential effects of stretch and compression on membrane currents and [Nat]c in ventricular myocytes. Prog Biophys Mol Biol, 2003, 82: 43–56, 1:CAS:528:DC%2BD3sXjsVaqurY%3D, 10.1016/S0079-6107(03)00004-X, 12732267
Johnson B D, Byerly L. A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+. Neuron, 1993, 10: 797–804, 1:CAS:528:DyaK3sXltlKjsr8%3D, 10.1016/0896-6273(93)90196-X, 8098608
Kiseleva I, Kamkin A, Wagner K D, et al. Mechanoelectric feedback after left ventricular infarction in rats. Cardiovas Res, 2000, 45: 370–378, 1:CAS:528:DC%2BD3cXotFKgtA%3D%3D, 10.1016/S0008-6363(99)00361-2
Fu L, Cao J X, Xie R S, et al. The effect of streptomycin on stretch-induced electrophysiological changes of isolated acute myocardial infarcted hearts in rats. Europace, 2007, 9: 578–584, 10.1093/europace/eum132, 17639065
Calaghan S C, Le Guennec J Y, White E. Cytoskeletal modulation of electrical and mechanical activity in cardiac myocytes. Prog Biophys Mol Biol, 2004, 84: 29–59, 1:CAS:528:DC%2BD3sXpt1Sqt7w%3D, 10.1016/S0079-6107(03)00057-9, 14642867
Parker K K, Taylor L K, Atkinson J B, et al. The effect of tubulin-binding agents on stretch-induced ventricular arrhythmias. Eur J Pharmacol, 2001, 417: 131–140, 1:CAS:528:DC%2BD3MXis1SjsLo%3D, 10.1016/S0014-2999(01)00856-1, 11301068
Galli A, DeFelice L J. Inactivation of L-type Ca channels in embryonic chick ventricle cells: dependence on the cytoskeletal agents colchicine and taxol. Biophys J, 1994, 67: 2296–2304, 1:CAS:528:DyaK2MXisVajtbk%3D, 10.1016/S0006-3495(94)80715-5, 7696470
Morris C E, Homann U. Cell surface area regulation and membrane tension. J Membr Biol, 2001, 179: 79–102, 1:CAS:528:DC%2BD3MXjvFGhu7w%3D, 11220366
Stiber J A, Seth M, Rosenberg P B. Mechanosensitive channels in striated muscle and the cardiovascular system: not quite a stretch anymore. J Cardiovasc Pharmacol, 2009, 54: 116–122, 1:CAS:528:DC%2BD1MXhtVWiu7bI, 10.1097/FJC.0b013e3181aa233f, 19597371
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Cao, J., Fu, L., Sun, D. et al. Taxol inhibits stretch-induced electrophysiological alterations in isolated rat hearts with acute myocardial infarction. Sci. China Life Sci. 53, 1009–1014 (2010). https://doi.org/10.1007/s11427-010-4039-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-010-4039-8