Protein kinase A-dependent phosphorylation of ryanodine receptors increases Ca2+ leak in mouse heart

被引：26

作者：

Morimoto, Satoshi ^{[1
,2
]}

O-Uchi, Jin ^{[2
,4
]}

Kawai, Makoto ^{[1
]}

Hoshina, Toshiyuki ^{[2
]}

Kusakari, Yoichiro ^{[2
]}

Komukai, Kimiaki ^{[1
]}

Sasaki, Hiroyuki ^{[3
]}

Hongo, Kenichi ^{[1
]}

Kurihara, Satoshi ^{[2
]}

机构：

[1] Jikei Univ, Div Cardiol, Sch Med, Minato Ku, Tokyo 1058461, Japan

[2] Jikei Univ, Dept Cell Physiol, Sch Med, Minato Ku, Tokyo 1058461, Japan

[3] Jikei Univ, Mol Cell Biol Div, Sch Med, Minato Ku, Tokyo 1058461, Japan

[4] Univ Rochester, Sch Med & Dent, Dept Med, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 390卷 / 01期

关键词：

Ca2+ leak; beta-Adrenoceptor stimulation; Ryanodine receptor; Protein kinase A; Ca2+/calmodulin-dependent protein kinase II; RETICULUM CALCIUM CONTENT; RAT VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; ALPHA(1)-ADRENOCEPTOR STIMULATION; DEFECTIVE REGULATION; PKA PHOSPHORYLATION; FAILURE; RELEASE; CHANNEL; PROGRESSION;

D O I：

10.1016/j.bbrc.2009.09.071

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In heart failure, chronic catecholaminergic stimulation increases diastolic Ca2+ leak from ryanodine receptors (RyRs) of sarcoplasmic reticulum (SR), possibly due to the phosphorylation of RyRs through the activation of protein kinase A (PKA) or Ca2+/calmodulin-dependent protein kinase II (CaMKII). In the present study, we attempted to identify which activated kinase is responsible for the enhanced Ca2+ leak caused by beta-adrenergic stimulation. Trabeculae obtained from the hearts of adult male C57BL/6J mice were treated with isoproterenol and then permeabilized with saponin. To examine SIR functions, Ca2+ in SR was released with caffeine and measured with fluo-3. The Ca2+ leak in isoproterenol-treated preparations was significantly increased when the PKA-dependent phosphorylation of RyR was increased without the involvement of CaMKII-dependent phosphorylation. Both the increase in Ca2+ leak and the phosphorylation of RyR were blocked by a PKA inhibitor. Our results show that beta-adrenergic stimulation increases Ca2+ leak from SR through PKA-dependent phosphorylation of RyR. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：87 / 92

页数：6

共 25 条

[1] Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure [J].