The overall objectives of the work are to obtain information concerning the structure and chemical properties of Z-discs from skeletal and heart muscle of several species, including humans. The studies will be done both on in vivo and on isolated Z-discs, and both on normal Z-discs and on "abnormal" Z-discs which are present in congestive heart failure, cardiac hypertrophy, and in various skeletal muscle diseases. For the coming grant period we wish to establish the most satisfactory way to isolate and purify, via zone electrophoresis or column chromatography, vertebrate Z-discs; to conduct, once the first goal is accomplished, the necessary ultrastructural and biochemical (including antibody) studies on isolated normal Z-discs; and to produce abnormal Z-discs in vertebrate skeletal and heart muscle, and perform the necessary structural and chemical comparison with normal Z-discs.