PMID- 12609973
OWN - NLM
STAT- MEDLINE
DCOM- 20030429
LR  - 20131121
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 92
IP  - 6
DP  - 2003 Apr 4
TI  - Calmodulin regulation of excitation-contraction coupling in cardiac myocytes.
PG  - 659-67
AB  - Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key 
      molecules involved in excitation-contraction (EC) coupling. In the present study, 
      we report that adenoviral expression of a mutant CaM lacking all of its four 
      Ca2+-binding sites, CaM(1-4), at a level 6.5-fold over endogenous CaM markedly 
      increases the amplitude and abbreviates the decay time of Ca2+ transients and 
      contraction in cultured rat ventricular myocytes. To determine the underlying 
      mechanisms, we examined the properties of L-type Ca2+ channels, 
      Ca2+/CaM-dependent protein kinase II (CaMKII), and phospholamban (PLB) in the 
      sarcoplasmic reticulum (SR). We found that CaM(1-4) expression markedly augmented 
      L-type Ca2+ current amplitude and slowed its inactivation. Surprisingly, 
      overexpression of CaM(1-4) increased CaMKII activity and phosphorylation of 
      PLB-Thr-17. Moreover, CaM(1-4) elevated diastolic Ca2+ and caffeine-labile Ca2+ 
      content of the SR. Inhibition of CaMKII by KN-93 or a myristoylated autocamtide-2 
      related inhibitory peptide prevented the aforementioned PLB phosphorylation and 
      reversed the positive inotropic and relaxant effects, indicating that CaMKII is 
      essential to CaM(1-4) actions. These results demonstrate that CaM modulates Ca2+ 
      influx, SR Ca2+ release, and Ca2+ recycling during cardiac EC coupling. A novel 
      finding of this study is that expression of a Ca2+-insensitive CaM mutant can 
      lead to activation of CaMKII in cardiac myocytes.
FAU - Yang, Dongmei
AU  - Yang D
AD  - National Laboratory of Biomembrane and Membrane Biotechnology, College of Life 
      Sciences, Peking University, Beijing, China.
FAU - Song, Long-Sheng
AU  - Song LS
FAU - Zhu, Wei-Zhong
AU  - Zhu WZ
FAU - Chakir, Khalid
AU  - Chakir K
FAU - Wang, Wei
AU  - Wang W
FAU - Wu, Caihong
AU  - Wu C
FAU - Wang, Yibin
AU  - Wang Y
FAU - Xiao, Rui-Ping
AU  - Xiao RP
FAU - Chen, S R Wayne
AU  - Chen SR
FAU - Cheng, Heping
AU  - Cheng H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030227
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Calmodulin)
RN  - 0 (phospholamban)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Channels, L-Type/physiology
MH  - Calcium Signaling
MH  - Calcium-Binding Proteins/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Calmodulin/analysis/genetics/*physiology
MH  - Cells, Cultured
MH  - Electric Conductivity
MH  - Mutation
MH  - *Myocardial Contraction
MH  - Myocytes, Cardiac/chemistry/metabolism/*physiology
MH  - Patch-Clamp Techniques
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sarcoplasmic Reticulum/metabolism
EDAT- 2003/03/01 04:00
MHDA- 2003/04/30 05:00
CRDT- 2003/03/01 04:00
PHST- 2003/03/01 04:00 [pubmed]
PHST- 2003/04/30 05:00 [medline]
PHST- 2003/03/01 04:00 [entrez]
AID - 01.RES.0000064566.91495.0C [pii]
AID - 10.1161/01.RES.0000064566.91495.0C [doi]
PST - ppublish
SO  - Circ Res. 2003 Apr 4;92(6):659-67. doi: 10.1161/01.RES.0000064566.91495.0C. Epub 
      2003 Feb 27.