[Inositol 1,4,5-triphosphate receptors (IP(3)Rs) in myocardial nuclei involved in pressure overload-induced hypertrophy of rat heart].
In order to clarify the importance of nuclear IP(3)Rs in the development of myocardial hypertrophy, a hypertensive rat model was established by abdominal aortic constriction, and velocity and isopyknic gradient centrifugation was employed to fractionate the cardiac nuclei. The maximal number of binding sites (B(max)) and dissociation constant (Kd) of IP(3) to the nuclear envelopes were measured by [(3)H] IP(3) binding assay. The existence of IP(3)Rs on myocardial nuclear envelope was confirmed. [Ca(2+)] inhibited [(3)H] IP(3) binding to its receptors in cardiac nuclear envelopes in a concentration-dependent way. Phosphorylation by CaM and endogenous PKC decreased B(max) of nuclear IP(3) receptors. B(max) and Kd of nuclear IP(3)Rs were increased by 1.217 (P<0.01) and by 2.149-fold (P<0.01) respectively in hypertrophic myocardium as compared with those of the control. The above results suggest that IP(3)Rs exist in myocardial nuclei and are down regulated by CaM, PMA and free Ca(2+). The increase of the binding sites of IP(3)Rs in the nuclear envelopes and the decrease of their affinity might play importment roles in the development of overload induction of cardiac hypertrophy.
Liu
J
J
Department of Cardiology, Xinqiao Hospital, Third Medical University, Chongqing 400037.
He
Z Y
ZY
Xu
S M
SM
Liu
F Y
FY
Wang
P Y
PY
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D015220:Calcium Channels; D002147:Calmodulin; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium