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

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. We investigated the effect of the anti-tumour drug taxol, a known microtubule polymerizing agent, on Ca²⁺ handling in adult rat ventricular myocytes. Treatment of cells with taxol caused proliferation of microtubules. 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. 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. 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.