Document Detail

Measurement and modeling of Ca2+ waves in isolated rabbit ventricular cardiomyocytes.
MedLine Citation:
PMID:  17545234     Owner:  NLM     Status:  MEDLINE    
The time course and magnitude of the Ca(2+) fluxes underlying spontaneous Ca(2+) waves in single permeabilized ventricular cardiomyocytes were derived from confocal Fluo-5F fluorescence signals. Peak flux rates via the sarcoplasmic reticulum (SR) release channel (RyR2) and the SR Ca(2+) ATPase (SERCA) were not constant across a range of cellular [Ca(2+)] values. The Ca(2+) affinity (K(mf)) and maximum turnover rate (V(max)) of SERCA and the peak permeability of the RyR2-mediated Ca(2+) release pathway increased at higher cellular [Ca(2+)] loads. This information was used to create a computational model of the Ca(2+) wave, which predicted the time course and frequency dependence of Ca(2+) waves over a range of cellular Ca(2+) loads. Incubation of cardiomyocytes with the Ca(2+) calmodulin (CaM) kinase inhibitor autocamtide-2-related inhibitory peptide (300 nM, 30 mins) significantly reduced the frequency of the Ca(2+) waves at high Ca(2+) loads. Analysis of the Ca(2+) fluxes suggests that inhibition of CaM kinase prevented the increases in SERCA V(max) and peak RyR2 release flux observed at high cellular [Ca(2+)]. These data support the view that modification of activity of SERCA and RyR2 via a CaM kinase sensitive process occurs at higher cellular Ca(2+) loads to increase the maximum frequency of spontaneous Ca(2+) waves.
N MacQuaide; J Dempster; G L Smith
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-01
Journal Detail:
Title:  Biophysical journal     Volume:  93     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-06     Completed Date:  2007-11-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2581-95     Citation Subset:  IM    
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
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MeSH Terms
Calcium / metabolism*
Calmodulin / metabolism
Computer Simulation
Fluorescent Dyes / pharmacology
Models, Biological
Muscle Cells / metabolism
Myocardium / metabolism
Myocytes, Cardiac / metabolism*
Ryanodine Receptor Calcium Release Channel / metabolism
Sarcoplasmic Reticulum / metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
Reg. No./Substance:
0/Calmodulin; 0/Fluorescent Dyes; 0/Ryanodine Receptor Calcium Release Channel; 7440-70-2/Calcium; EC Reticulum Calcium-Transporting ATPases

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