Parvalbumin isoforms differentially accelerate cardiac myocyte relaxation kinetics in an animal model of diastolic dysfunction

David W. Rodenbaugh, Wang Wang, Jennifer Davis, Terri Edwards, James D. Potter, Joseph M. Metzger

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16 Scopus citations

Abstract

The cytosolic Ca2+/Mg2+-binding protein α-parvalbumin (α-Parv) has been shown to accelerate cardiac relaxation; however, beyond an optimal concentration range, α-Parv can also diminish contractility. Mathematical modeling suggests that increasing Parv's Mg2+ affinity may lower the effective concentration of Parv ([Parv]) to speed relaxation and, thus, limit Parv-mediated depressed contraction. Naturally occurring α/β-Parv isoforms show divergence in amino acid primary structure (57% homology) and cation-binding affinities, with β-Parv having an estimated 16% greater Mg2+ affinity and ∼200% greater Ca2+ affinity than α-Parv. We tested the hypothesis that, at the same or lower estimated [Parv], mechanical relaxation rate would be more significantly accelerated by β-Parv than by α-Parv. Dahl salt-sensitive (DS) rats were used as an experimental model of diastolic dysfunction. Relaxation properties were significantly slowed in adult cardiac myocytes isolated from DS rats compared with controls: time from peak contraction to 50% relaxation was 57 ± 2 vs. 49 ± 2 (SE) ms (P < 0.05), validating this model system. DS cardiac myocytes were subsequently transduced with α- or β-Parv adenoviral vectors. Upon Parv gene transfer, β-Parv caused significantly faster relaxation than α-Parv (P < 0.05), even though estimated [β-Parv] was ∼10% of [α-Parv]. This comparative analysis showing distinct functional outcomes raises the prospect of utilizing naturally occurring Parv variants to address disease-associated slowed cardiac relaxation.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number3
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Keywords

  • Gene transfer
  • Mechanical relaxation

ASJC Scopus subject areas

  • Physiology

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