Measurement and modeling of Ca2+ waves in isolated rabbit ventricular cardiomyocytes

MacQuaide, N. , Dempster, J. and Smith, G.L. (2007) Measurement and modeling of Ca2+ waves in isolated rabbit ventricular cardiomyocytes. Biophysical Journal, 93(7), pp. 2581-2595. (doi: 10.1529/biophysj.106.102293) (PMID:17545234) (PMCID:PMC1965444)

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The time course and magnitude of the Ca2+ fluxes underlying spontaneous Ca2+ waves in single permeabilized ventricular cardiomyocytes were derived from confocal Fluo-5F fluorescence signals. Peak. ux rates via the sarcoplasmic reticulum (SR) release channel (RyR2) and the SR Ca2+ ATPase (SERCA) were not constant across a range of cellular [Ca2+] values. The Ca2+ affinity (K-mf) and maximum turnover rate (V-max) of SERCA and the peak permeability of the RyR2-mediated Ca2+ release pathway increased at higher cellular [Ca2+] loads. This information was used to create a computational model of the Ca2+ wave, which predicted the time course and frequency dependence of Ca2+ waves over a range of cellular Ca 21 loads. Incubation of cardiomyocytes with the Ca2+ calmodulin (CaM) kinase inhibitor autocamtide-2-related inhibitory peptide (300 nM, 30 mins) significantly reduced the frequency of the Ca2+ waves at high Ca2+ loads. Analysis of the Ca2+ fluxes suggests that inhibition of CaM kinase prevented the increases in SERCA Vmax and peak RyR2 release. ux observed at high cellular [ Ca 21]. These data support the view that modi. cation of activity of SERCA and RyR2 via a CaM kinase sensitive process occurs at higher cellular Ca2+ loads to increase the maximum frequency of spontaneous Ca2+ waves.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Dempster, Mr John and MacQuaide, Dr Niall
Authors: MacQuaide, N., Dempster, J., and Smith, G.L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Biophysical Journal
ISSN (Online):1542-0086
Published Online:04 November 2008

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