Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient and L‐type Ca2+ current in rat ventricular myocytes

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Abstract
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.