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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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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Inbred Dahl Rats
Parvalbumins
Cardiac Myocytes
Protein Isoforms
Animal Models
Cations
Carrier Proteins
Theoretical Models
Salts
Amino Acids
Genes

Keywords

  • Gene transfer
  • Mechanical relaxation

ASJC Scopus subject areas

  • Physiology

Cite this

Parvalbumin isoforms differentially accelerate cardiac myocyte relaxation kinetics in an animal model of diastolic dysfunction. / Rodenbaugh, David W.; Wang, Wang; Davis, Jennifer; Edwards, Terri; Potter, James D.; Metzger, Joseph M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 3, 01.09.2007.

Research output: Contribution to journalArticle

Rodenbaugh, David W. ; Wang, Wang ; Davis, Jennifer ; Edwards, Terri ; Potter, James D. ; Metzger, Joseph M. / Parvalbumin isoforms differentially accelerate cardiac myocyte relaxation kinetics in an animal model of diastolic dysfunction. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 3.
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