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

1. Microtubules form part of the cytoskeleton. Their role in adult ventricu lar 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 microt ubule polymerizing agent, on Ca2+ handling in adult rat ventricular myocyte s. 3. Treatment of cells with taxol caused proliferation of microtubules. 4. In taxol-treated cells there was a reduction in the amplitude of contrac tion, 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 i s consistent with the hypothesis that taxol reduces fractional SR Ca2+ rele ase. 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 ma y be important regulators of Ca2+ handling in the heart.