Journal article
Suppression of dynamic Ca2+ transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition
Journal of molecular and cellular cardiology, Vol.40(2), pp.213-223
02/2006
DOI: 10.1016/j.yjmcc.2005.11.005
PMID: 16413575
Abstract
The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is important for regulating L-type Ca2+ current (ICa) and cytoplasmic Ca2+ (Ca2+i) uptake and release from the sarcoplasmic reticulum (SR), key elements of the ‘Ca2+-induced Ca2+ release’ (CICR) mechanism. However, the effects of chronic CaMKII inhibition on Ca2+i responses during CICR are unknown. We hypothesized that chronic CaMKII inhibition significantly affects CICR in ventricular myocytes. We studied CICR by simultaneously measuring Ca2+i transients and ICa in voltage-clamped ventricular myocytes isolated from a recently developed genetic mouse model of cardiac CaMKII inhibition. These measurements were repeated in ventricular myocytes from novel mice with cardiac CaMKII inhibition lacking phospholamban (PLN), a known CaMKII substrate and a negative regulator of Ca2+i uptake into the SR Ca2+ store. CaMKII inhibition eliminated a pattern of ICa increases called facilitation and significantly reduced beat-to-beat and cell-to-cell variability of peak Ca2+i transients in ventricular myocytes with PLN. PLN ablation eliminated ICa facilitation even in the absence of CaMKII inhibition and the effects of CaMKII inhibition to reduce SR Ca2+ content and slow SR Ca2+ uptake were lost in the absence of PLN. PLN ablation significantly reduced ICa beat-to-beat variability in cells with CaMKII inhibition. These findings show that chronic CaMKII inhibition reduces variability of CICR responses in a manner that is partly dependent on the presence of PLN.
Details
- Title: Subtitle
- Suppression of dynamic Ca2+ transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition
- Creators
- Yuejin WuAyumi ShintaniChad GrueterRong ZhangYue HouJinying YangEvangelia G KraniasRoger J ColbranMark E Anderson
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.40(2), pp.213-223
- DOI
- 10.1016/j.yjmcc.2005.11.005
- PMID
- 16413575
- NLM abbreviation
- J Mol Cell Cardiol
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Language
- English
- Date published
- 02/2006
- Academic Unit
- Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
- Record Identifier
- 9984094772802771
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