Optimal range for parvalbumin as relaxing agent in adult cardiac myocytes: Gene transfer and mathematical modeling

Pierre Coutu, Joseph M. Metzger

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Parvalbumin (PV) has recently been shown to increase the relaxation rate when expressed in intact isolated cardiac myocytes via adenovirus gene transfer. We report here a combined experimental and mathematical modeling approach to determine the dose-response and the sarcomere length (SL) shortening-frequency relationship of PV in adult rat cardiac myocytes in primary culture. The dose-response was obtained experimentally by observing the PV-transduced myocytes at different time points after gene transfer. Calcium transients and unloaded mechanical contractions were measured. The results were as follows. At low estimated [PV] (∼0.01 mM), contractile parameters were unchanged; at intermediate [PV], relaxation rate of the mechanical contraction and the decay rate of the calcium transient increased with little effects on amplitude; and at high [PV] (∼0.1 mM), relaxation rate was further increased, but the amplitudes of the mechanical contraction and the calcium transient were diminished when compared with control myocytes. The SL shortening-frequency relationship exhibited a biphasic response to increasing stimulus frequency in controls (decrease in amplitude and relengthening time from 0.2 to 1.0 Hz followed by an increase in these parameters from 2.0 to 4.0 Hz). The effect of PV was to flatten this frequency response. This flattening effect was partly explained by a reduction in the variation in fractional binding of PV to calcium during beats at high frequency. In conclusion, experimental results and mathematical modeling indicate that there is an optimal PV range for which relaxation rate is increased with little effect on contractile amplitude and that PV effectiveness decreases as the stimulus frequency increases.

Original languageEnglish (US)
Pages (from-to)2565-2579
Number of pages15
JournalBiophysical journal
Volume82
Issue number5
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
This study was supported by grants from the National Institutes of Health and the American Heart Association.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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