ABSTRACT
This study, performed on pure muscular regulatory proteins and contracting myocytes in embryonal myocardial cultures, showed a direct interaction of the tropomyosin-troponin complex (TM-TN) with beta-adrenergic and Ca2+-channel-blocking agents. The TM-TN complex incorporates into the myocyte membranes as well as into artificial membranes, inducing changes in the X-ray diffraction picture. This protein complex prevents the inhibitory effect of D-600, propranolol, and other agents on the contraction of myocytes, restores the sensitivity of the cells to catecholamines, and promotes transmembrane transport of Ca2+ . beta-Adrenergic agents decrease the melting point and increase the intramolecular mobility of the TM-TN complex. They activate the Mg2+ ATPase of native but not desensitized actomyosin. In this case, they do not compete with Ca2+ for the same sites. The role of the direct interaction of cardioactive agents with the Ca2+-binding proteins in the membranes and other compartments of the cell is discussed in connection with their mechanism of action on the myocardium.
