Cytochalasin B and embryonic heart muscle: contractility, excitability and ultrastructure.

The effect of cytochalasin B (CB) on beating, electrical activity and cytological ultrastructure of embryonic hearts and tissue-cultured heart preparations was investigated. The inhibition of spontaneous pulsation and the subsequent recovery after drug washout were found to be dosedependent and to be a function of the type of preparation. In the presence of CB, spontaneous action potentials can be recorded from all three (intact hearts, isolated myocytes, reaggregated cells) after cessation of all visible contractions, although the action potential duration is reduced. CB at 0-5-10 /ig/ml was found not to uncouple heart cells electrically nor to prevent cells from aggregating and establishing new electrical coupling. In all 3 systems, however, CB does result in disruption of myofibrillar organization. After 30 h in CB (2 /ig/ml) bundles of myofiJaments are found to be randomly oriented, with Z-band material condensed into amorphous bodies, no longer aligned with the myofibril, but remaining in register between the A-bands. Within the bundles the normal hexagonal cross-section of thick and thin filaments is maintained. The unaligned Z-bodies, however, demonstrate attached thin filaments of very reduced length. Following washout of the drug, normal sarcomeric organization is restored in parallel -with resumption of spontaneous beating. The present data, therefore, are consistent with the hypothesis that one major effect of CB is an alteration in myofibril (myofilament) stability, and that this effect alone is sufficient to account for the observed inhibition of contractility.