Role of load in regulating eIF-4F complex formation in adult feline cardiocytes

This study examined whether cardiocyte load increases eIF-4F complex format ion. To increase load in vitro, adult feline cardiocytes were electrically stimulated to contract (1 Hz, 5-ms pulses). eIF-4F complex formation, measu red by eIF-4G association with eIF-4E, increased 57 +/- 16% after 4 h of co ntraction compared with controls. eIF-4F complex formation did not increase on electrical stimulation with 2,3-butanedione monoxime (BDM), an inhibito r of active tension. Both insulin and phorbol ester increased eIF-4F comple x formation, but these increases were unaffected by BDM. Insulin caused a s hift of eIF-4E binding proteins (4E-BPs) into their hyperphosphorylated gam ma-isoforms and dissociation of 4E-BPs from eIF-4E. Rapamycin inhibited 4E- BP phosphorylation in response to insulin but had no effect on eIF-4F compl ex formation. Electrically stimulated contraction caused a partial shift of 4E-BP1 and 4E-BP2 into the gamma-isoforms, but it had no effect on 4E-BP a ssociation with eIF-4E. Rapamycin blocked the increase in eIF-4F complex fo rmation in electrically stimulated cardiocytes and depressed contractility. These data indicate that cardiocyte load causes a tension-dependent increa se in eIF-4F complex formation that does not require dissociation of 4E-BPs from eIF-4E.