Role of microtubules in the viscoelastic properties of isolated cardiac muscle

Myocardial viscoelastic properties are determined by both interstitial collagens and intramocyte structures, including sarcolemma, contractile proteins and the cytoskeleton. It is not known whether myocyte microtubules are significant constituents that contribute to the viscoelastic properties of cardiac muscle. We examined the passive properties of isolated right-ventricular papillary muscles before and after altering the polymerization states of microtubules. The muscles were subjected to sinusoidal changes in length (strain) and the resultant changes in resting tension (stress) were measured. The elastic constant was determined by the slope of the stress-strain relation during the slow increase in muscle length (duration 60s). The viscous constant was determined by the loop area between the stress-strain relation obtained during the rapid increase and decrease in muscle length (duration 1 s). Colchicine (1 μmol/l, 1 h), which depolymerized microtubules, had little effect on either the elastic constant or viscous constant. In contrast, taxol (10 μmol/l), which hyperpolymerized and stabilized microtubules, exerted a time-dependent increase in the viscous constant (133 ± 9% of control; n = 9, P < 0.05), but did not affect the elastic constant (18.9 ± 2.2 to 17.7 ± 2.1; n = 7, P = N.S.). The increase of viscosity by taxol closely paralleled the increase in the strain rate. The specificity of each pharmacological intervention for the microtubule polymerization state was confirmed by both a Western blot analysis and the immunofluorescence micrographs of myocyte tubulin. Like other cytoskeleton and extracellular collagens, the increase in the myocyte microtubule density was able to modify the viscous component of the passive properties of the isolated cardiac muscle.