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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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.
| Creators(s): |
MacQuaide, N., Dempster, J.  ORCID: https://orcid.org/0000-0003-2199-2945 and Smith, G.L.;
| 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: | 20 Jan 2021 17:33 |
| URI: | https://strathprints.strath.ac.uk/id/eprint/4937 |
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