Fig. 4.

Membrane integrity and the micro-environment of cardiac sarcomeres. Sarcomeres are depicted in association with mechano-sensitive elements in a network of stress sensors including microtubules, Z-disk (with docked signaling molecules), M-band (with a terminal titin kinase), and costamere proteins(vinculin (Vin), paxillin (Pax),focal adhesion kinase (FAK), contiguous with extra-cellular matrix (ECM) -integrin signaling networks (via tensin and tailin). The dystroglycan/sarcoglycan complex is linked to these networks as shown and with dysferlin/caveolin at the t-tubule are major controllers of sarcolemma fragility. Included in the sarcomere micro-environment are mitochondria, and membrane elements (sarcomlemma, t-tubules and sarcoplasmic reticulum) controlling excitation and Ca-fluxes to and from the myofilaments. The illustration depicts the transit of cTn from thin filaments and sarcoplasm to blood and lymphatic capillaries related to AMI-induced membrane bleb formation and rupture and to membrane fragility associated with mechanical stressors. Note that mechnano-sensitive transcription factors at the Z-disk shuttle to and from the nucleus. There is also entry of cTnI and cTnT into the nuclear compartment, where they appear to function in epigenetic regulation that may be maladaptive. See text for discussion.