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.