Journal article
Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy
Circulation research, Vol.97(5), pp.457-464
09/02/2005
DOI: 10.1161/01.RES.0000179722.79295.d4
PMID: 16051885
Abstract
In conscious dogs with severe left ventricular (LV) hypertrophy (H) (doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca2+. There was no change in L-type Ca2+ channel current (ICa) density but the ability of ICa to trigger Ca2+ release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na+/Ca2+ exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca2+ sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca2+ load. A higher Ca2+ spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca2+ content. However, Ca2+ waves were found to be less frequent, slower and were more likely to be aborted in Ca2+-challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca2+ distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca2+ load. We conclude that severe LVH with compensation masks cellular and subcellular Ca2+ defects that remain likely contributors to the limited contractile reserve of LVH.
Details
- Title: Subtitle
- Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy
- Creators
- Long-Sheng Song - Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USAYeqing PiSong-Jung KimAtsuko YataniSilvia GuatimosimRaymond K KudejQingxiu ZhangHeping ChengLuc HittingerBijan GhalehDorothy E VatnerW Jonathan LedererStephen F Vatner
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.97(5), pp.457-464
- DOI
- 10.1161/01.RES.0000179722.79295.d4
- PMID
- 16051885
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Grant note
- 1PO1HL69020 / NHLBI NIH HHS 5R01HL62442 / NHLBI NIH HHS 5R01HL025675 / NHLBI NIH HHS 5R01HL65182 / NHLBI NIH HHS 2PO1HL59139 / NHLBI NIH HHS 5P01HL070709 / NHLBI NIH HHS 2R01AG14121 / NIA NIH HHS HL65182 / NHLBI NIH HHS Intramural NIH HHS HL65183 / NHLBI NIH HHS AG023137 / NIA NIH HHS 2R01HL33107 / NHLBI NIH HHS 5P01HL067849 / NHLBI NIH HHS 5R01HL65183 / NHLBI NIH HHS 2R01HL036974 / NHLBI NIH HHS
- Language
- English
- Date published
- 09/02/2005
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094754702771
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