Excessive microtubules are not responsible for depressed force per cross-bridge in cardiac neural-crest-ablated embryonic chick hearts

Ablation of the cardiac neural crest (CNCA) in embryonic chicks results in a high incidence of persistent truncus arteriosus, a congenital heart defec t associated with decreased myocardial contractility. Using left ventricula r trabeculae from chicks at embryonic day (ED) 15, we have previously shown that the twitch force of intact preparations is significantly reduced wher eas the maximal calcium-activated force of skinned preparations is not sign ificantly different in CNCA and sham-operated animals. We also previously f ound that the ventricular content of myosin, as well as of actin and tropom yosin, was nearly doubled in ED 15 hearts after CNCA. Since the number of c ross-bridges is proportional to the myosin concentration, these data sugges t that the force exerted per cross-bridge is decreased in CNCA hearts. We i nvestigated the possibility that the decrease in force per cross-bridge is caused by inhibition of the contractile apparatus by excessive microtubules . To the contrary, we found that the total P-tubulin content and the fracti on of P-tubulin polymerized in microtubules measured by Western blotting wa s the same in ventricular muscle strips from CNCA and sham-operated embryos . Furthermore, exposure to microtubule-destabilizing agents did not improve the force-producing capability of the contractile apparatus in CNCA embryo s. We conclude that depression of force per cross-bridge in hearts from CNC A embryos is not due to an excess of microtubules.