Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor

被引：523

作者：

Wehrens, XHT ^{[1
]}

Lehnart, SE ^{[1
]}

Reiken, SR ^{[1
]}

Marks, AR ^{[1
]}

机构：

[1] Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA

来源：

CIRCULATION RESEARCH | 2004年 / 94卷 / 06期

关键词：

ryanodine receptor; calcium Ca2+/calmodulin-dependent kinase II protein kinase A; heart failure;

D O I：

10.1161/01.RES.0000125626.33738.E2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Using site-directed mutagenesis, we identified the specific Ca2+/calmodulin-dependent protein kinase II ( CaMKII) phosphorylation site on recombinant RyR2, distinct from the site for protein kinase A (PKA) that mediates the "fight-or-flight" stress response. CaMKII phosphorylation increased RyR2 Ca2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca2+-induced Ca2+ release. Moreover, rate-dependent CaMKII phosphorylation of RyR2 was defective in heart failure. CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available onlineathttp://circres.ahajournals.org.

引用

页码：E61 / E70

页数：10

共 59 条

[1] Cardiac excitation-contraction coupling [J].

Bers, DM .

NATURE, 2002, 415 (6868) :198-205

[2]

Bowditch H. P., 1871, ARB PHYSL ANSTALT LE, V6, P139

[3] Type 1 phosphatase, a negative regulator of cardiac function [J].

Carr, AN ;

Schmidt, AG ;

Suzuki, Y ;

del Monte, F ;

Sato, Y ;

Lanner, C ;

Breeden, K ;

Jing, SL ;

Allen, PB ;

Greengard, P ;

Yatani, A ;

Hoit, BD ;

Grupp, IL ;

Hajjar, RJ ;

DePaoli-Roach, AA ;

Kranias, EG .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (12) :4124-4135

[4] Frequency-dependent acceleration of relaxation in the heart depends on CaMKII, but not phospholamban [J].

DeSantiago, J ;

Maier, LS ;

Bers, DM .

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2002, 34 (08) :975-984

[5] Effects of PP1/PP2A inhibitor calyculin A on the E-C coupling cascade in murine ventricular myocytes [J].

Dubell, WH ;

Gigena, MS ;

Guatimosim, S ;

Long, XL ;

Lederer, WJ ;

Rogers, TB .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (01) :H38-H48

[6] Dynamic modulation of excitation-contraction coupling by protein phosphatases in rat ventricular myocytes [J].

duBell, WH ;

Lederer, WJ ;

Rogers, TB .

JOURNAL OF PHYSIOLOGY-LONDON, 1996, 493 (03) :793-800

[7] RETRACTED: Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels (Retracted Article) [J].

Dzhura, I ;

Wu, YJ ;

Colbran, RJ ;

Balser, JR ;

Anderson, ME .

NATURE CELL BIOLOGY, 2000, 2 (03) :173-177

[8] Ca2+/calmodulin-dependent kinase II phosphorylates the epidermal growth factor receptor on multiple sites in the cytoplasmic tail and serine 744 within the kinase domain to regulate signal generation [J].

Feinmesser, RL ;

Wicks, SJ ;

Taverner, CJ ;

Chantry, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (23) :16168-16173

[9] FKBP12 binding modulates ryanodine receptor channel gating [J].

Gaburjakova, M ;

Gaburjakova, J ;

Reiken, S ;

Huang, F ;

Marx, SO ;

Rosemblit, N ;

Marks, AR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :16931-16935

[10]

GINSBURG KS, 2004, J PHYSL 0114

← 1 2 3 4 5 6 →