Stretch-induced inositol trisphosphate and tetrakisphosphate production in rat cardiomyocytes.

The kinetics and signal transduction of inositol phosphate production were studied after a 20% stretch of neonatal rat cardiomyocytes in culture. Inositol trisphosphate (IP3) production was increased by 41% above control after 10-20 s of cellular stretch but returned to control after 120 s of stretch. The increase in IP3 was potentiated in high K+ medium and was inhibited by pertussis toxin, suggesting the existence of a pertussis toxin-sensitive G protein in signal transduction. Ion-pair HPLC analysis of cell extracts stretched for 20 s showed an increase in both IP3 isomers, mostly 1,4,5-IP3 (+66%) with a weak increase in IP4 (+10%), whereas 120 s stretch induced an increase in IP4 (+26% above control) associated with a decrease of 1,4,5-IP3 isomer as compared with 20 s stretch. It is concluded that the progressive increase in IP4 production associated with an early rise in IP3 after stretching myocardial cells may be a factor inducing the length-dependent activation of cardiac muscle through a modulation of intracellular free calcium concentration.