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Effect of the microtubule polymerizing agent taxol on contraction, Ca 2+ transient and L‐type Ca 2+ current in rat ventricular myocytes
Author(s) -
Howarth F. C.,
Calaghan S. C.,
Boyett M. R.,
White E.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0409v.x
Subject(s) - microtubule , caffeine , myocyte , endoplasmic reticulum , contraction (grammar) , biophysics , calcium , cytoskeleton , chemistry , inotrope , biology , endocrinology , cell , microbiology and biotechnology , biochemistry , organic chemistry
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 Ca 2+ 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 Ca 2+ current, but a significant reduction in the amplitude of the Ca 2+ transient. 5 Caffeine was used to release Ca 2+ from the sarcoplasmic reticulum (SR). There was a significant reduction in the ratio of electrically stimulated : caffeine‐induced Ca 2+ transients in taxol‐treated cells. This observation is consistent with the hypothesis that taxol reduces fractional SR Ca 2+ release. 6 We suggest that the negative inotropic effect of taxol may, at least in part, be the result of reduced release of Ca 2+ from the SR. Microtubules may be important regulators of Ca 2+ handling in the heart.