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.
Dassouli
A
A
Unité INSERM U.2, Faculté de Médecine, Creteil, France.
Sülpice
J C
JC
Roux
S
S
Crozatier
B
B
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D008465:Mechanoreceptors / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; C081655:inositol-1,3,4,5-tetrakisphosphate; D011189:Potassium Chloride; D015544:Inositol 1,4,5-Trisphosphate; C058097:inositol 1,3,4-trisphosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D009638:Norepinephrine