Role of microtubules in the contractile dysfunction of myocytes from tachycardia-induced dilated cardiomyopathy

Masaru Takahashi, Hiroyuki Tsutsui, Shintaro Kinugawa, Keiko Igarashi-Saito, Shimako Yamamoto, Mitsutaka Yamamoto, Hirofumi Tagawa, Kyoko Imanaka-Yoshida, Kensuke Egashira, Akira Takeshita

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    28 Citations (Scopus)


    Microtubules of cardiac myocytes are increased in pressure-overloaded cardiac hypertrophy, which interfere with the actin-myosin crossbridge motion and depress muscle contractility. However, it is unknown whether microtubules are increased in non-hypertrophied, dilated cardiomyopathy and, if so, their increase could contribute to the depressed contractility. We assessed the contractile function of isolated left-ventricular (LV) myocytes and also quantitated tubulin mRNA levels as well as free and polymerized tubulin proteins using the LV myocardium obtained from dogs with rapid pacing (240 beats/min, 4 weeks)-induced dilated failing cardiomyopathy (HF; n = 6) and control dogs (n = 6). Myocyte contractility was significantly depressed in HF compared to control. Northern blot analysis indicated that tubulin mRNA levels (normalized to GAPDH mRNA) in HF dogs were upregulated (0.43 ± 0.04 v 0.13 ± 0.02; P < 0.01). In contrast, the amount of total tubulins (633 ± 52 v 697 ± 42 μg/g wet weight; P = N.S.) and the ratio of polymerized tubulin fraction-to-total tubulin (0.44 ± 0.02 v 0.44 ± 0.01; P = N.S.) did not differ between the two groups. Immunohistochemical studies showed no apparent differences in the distribution or density of intracellular microtubule network. Further, the exposure of myocytes to colchicine (1 μmol/l, 30 min), which depolymerizes microtubules, did not promote any improvement of the depressed myocyte contraction. Pacing-induced tachycardia increased myocardial tubulin mRNA, but the amount of total and polymerized tubulins were not increased, indicating that alterations in myocyte microtubules do not contribute to the contractile abnormalities in this model of HF.

    Original languageEnglish
    Pages (from-to)1047-1057
    Number of pages11
    JournalJournal of Molecular and Cellular Cardiology
    Issue number5
    Publication statusPublished - May 1998

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Cardiology and Cardiovascular Medicine


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