Journal article
Differential effects of phospholamban and Ca2+/calmodulin-dependent kinase II on [Ca2+]i transients in cardiac myocytes at physiological stimulation frequencies
American journal of physiology. Heart and circulatory physiology, Vol.294(5), pp.H2352-2362
05/2008
DOI: 10.1152/ajpheart.01398.2006
PMID: 18359893
Abstract
In cardiac myocytes, the activity of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is hypothesized to regulate Ca(2+) release from and Ca(2+) uptake into the sarcoplasmic reticulum via the phosphorylation of the ryanodine receptor 2 and phospholamban (PLN), respectively. We tested the role of CaMKII and PLN on the frequency adaptation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) transients in nearly 500 isolated cardiac myocytes from transgenic mice chronically expressing a specific CaMKII inhibitor, interbred into wild-type or PLN null backgrounds under physiologically relevant pacing conditions (frequencies from 0.2 to 10 Hz and at 37 degrees C). When compared with that of mice lacking PLN only, the combined chronic CaMKII inhibition and PLN ablation decreased the maximum Ca(2+) release rate by more than 50% at 10 Hz. Although PLN ablation increased the rate of Ca(2+) uptake at all frequencies, its combination with CaMKII inhibition did not prevent a frequency-dependent reduction of the amplitude and the duration of the [Ca(2+)](i) transient. High stimulation frequencies in the physiological range diminished the effects of PLN ablation on the decay time constant and on the maximum decay rate of the [Ca(2+)](i) transient, indicating that the PLN-mediated feedback on [Ca(2+)](i) removal is limited by high stimulation frequencies. Taken together, our results suggest that in isolated mouse ventricular cardiac myocytes, the combined chronic CaMKII inhibition and PLN ablation slowed Ca(2+) release at physiological frequencies: the frequency-dependent decay of the amplitude and shortening of the [Ca(2+)](i) transient occurs independent of chronic CaMKII inhibition and PLN ablation, and the PLN-mediated regulation of Ca(2+) uptake is diminished at higher stimulation frequencies within the physiological range.
Details
- Title: Subtitle
- Differential effects of phospholamban and Ca2+/calmodulin-dependent kinase II on [Ca2+]i transients in cardiac myocytes at physiological stimulation frequencies
- Creators
- Andreas A Werdich - Department of Biomedical Engineering, Vanderbilt University, 6301 Stevenson Center, VU Station B 351631, Nashville, TN 37235-1631, USAEduardo A LimaIgor DzhuraMadhu V SinghJingdong LiMark E AndersonFranz J Baudenbacher
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.294(5), pp.H2352-2362
- DOI
- 10.1152/ajpheart.01398.2006
- PMID
- 18359893
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- U01 AI061223 / NIAID NIH HHS HL 070250 / NHLBI NIH HHS HL 062494 / NHLBI NIH HHS HL 046681 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/2008
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094388002771
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