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We have shown that Y-27632, an inhibitor of Rho-associated kinase (ROCK), delays sarcomere assembly in cultured rat neonatal cardiomyocytes pretreated with angiotensin II. Y-27632 affects the beat rate of cardiomyocytes, but this effect is only observed at high cell density and, therefore, seems to be related to impairment of cell-cell interactions. Consistent with this suggestion, ROCK2 is localized in myofibrillar Z-disks of human myocardium as well as in intercalated disks. We propose that ROCK participates in maturation of the myocardial contractile system through phosphorylation of its molecular targets in Z-disks and in intercalated disks.

Using the immunofluorescence approach, we have determined that the recently detected protein kinases, among which are RhoA-activated kinase, integrin-linked kinase, zipper interacting protein kinase, and death-associated protein kinase, are capable of phosphorylating myosin localized in the Z-lines of human myocardial sarcomeres. Additionally, we studied the content of integrin-linked and zipper interacting protein kinases in human embryonic myocardium, as well as in normal and hypertrophic adult human heart. The content of these protein kinases in adult normal myocardium increases in comparison with the embryonic heart. The content of integrin-linked and zipper interacting protein kinases in hypertrophic myocardium is higher as compared with the normal adult heart. The data obtained suggest the involvement of these protein kinases in the development and hypertrophy of the human heart.