Effect of the microtubule polymerizing agent taxol on contraction, Ca<SUP>2+</SUP> transient and L-type Ca<SUP>2+</SUP> current in rat ventricular myocytes

作     者：Howarth, FC Calaghan, SC Boyett, MR White, E 

作者机构：Univ Leeds Sch Biomed Sci Leeds LS2 9JT W Yorkshire England 

出 版 物：《JOURNAL OF PHYSIOLOGY-LONDON》 (生理学杂志)

年 卷 期：1999年第516卷第2期

页      面：409-419页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

主　　题：抗肿瘤药 植物/药理学 咖啡因/药理学 钙通道/药物作用 钙通道/代谢 钙通道 L型 钙信号/药物作用 秋水仙碱/药理学 抑制 化学性 电刺激 心室/细胞学 心室/药物作用 心室/超微结构 微管/药物作用 微管/超微结构 心肌收缩/药物作用 心肌/细胞学 心肌/代谢 心肌/超微结构 紫杉酚/药理学 膜片钳术 磷酸二酯酶抑制剂/药理学 大鼠 Wistar 肌浆网/药物作用 肌浆网/代谢 动物 男(雄)性 大鼠 

摘      要：1. Microtubules form part of the cytoskeleton. Their role in adult ventricular myocytes is not well understood although microtubule proliferation has previously been linked with reduced contractile function. 2. We investigated the effect of the anti-tumour drug taxol, a known microtubule polymerizing agent, on Ca2+ handling in adult rat ventricular myocytes. 3. Treatment of cells with taxol caused proliferation of microtubules. 4. In taxol-treated cells there was a reduction in the amplitude of contraction, no significant effect on the amplitude of L-type Ca2+ current, but a significant reduction in the amplitude of the Ca2+ transient. 5. Caffeine was used to release Ca2+ from the sarcoplasmic reticulum (SR). There was a significant reduction in the ratio of electrically stimulated: caffeine-induced Ca2+ transients in taxol-treated cells. This observation is consistent with the hypothesis that taxol reduces fractional SR Ca2+ release. 6. We suggest that the negative inotropic effect of taxol may, at least in part, be the result of reduced release of Ca2+ from the SR. Microtubules may be important regulators of Ca2+ handling in the heart.