Hypertrophy alters effect of Ins(1,4,5)P3 on Ca2+ release in skinned rat heart muscle.
The effects of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] on the ability of the sarcoplasmic reticulum (SR) to accumulate and release Ca2+ and on the Ca2+ sensitivity of the contractile proteins were investigated using chemically (saponin) skinned cardiac fibers (60-120 microns diam) obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 3-6 wk before study. Age- and weight-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio by 45%. Ins(1,4,5)P3 at a concentration of 10 microM did not change the Ca(2+)-tension relationship at Ca2+ concentrations of 10(-7) to 10(-5) M in either normal or hypertrophied fibers. Ins(1,4,5)P3 also did not influence Ca2+ uptake by the SR in either normal or hypertrophied fibers. Ins(1,4,5)P3 did not induce Ca2+ release from the SR directly in either group. However, pretreatment with Ins(1,4,5)P3 enhanced the 5 mM caffeine-induced Ca2+ release by 80.5 +/- 22.7% in normal fibers enhances, rather than directly induces, SR Ca2+ release in normal rat hearts and that sustained pressure overload diminishes the response of the SR Ca(2+)-release system to Ins(1,4,5)P3, an action that may be partly responsible for contractile dysfunction in cardiac hypertrophy.
Furukawa
N
N
Department of Medicine (Division of Cardiology), University of Miami School of Medicine, Florida 33101.
Bassett
A L
AL
Furukawa
T
T
Myerburg
R J
RJ
Kimura
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006652:Histological Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium