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

MacQuaide, N. and Dempster, J. and Smith, G.L. (2007) Measurement and modelling of Ca2+ waves in isolated rabbit ventricular cardiomyocytes. Biophysical Journal, 93 (7). pp. 2581-2595. ISSN 0006-3495

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Abstract

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 flux 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 (Kmf) and maximum turnover rate (Vmax) 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 Ca2+ 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 flux observed at high cellular [Ca2+]. These data support the view that modification 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: Article
ID code: 4937
Keywords: biophysics, cardiomyocytes, Ca2+ waves, Pharmacy and materia medica, Biophysics
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Strathprints Administrator
Date deposited: 30 Nov 2007
Last modified: 22 Mar 2017 09:49
URI: https://strathprints.strath.ac.uk/id/eprint/4937
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