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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1705    most recent 00232.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rodenbaugh, D. W. Articles by Metzger, J. M. Search for Related Content PubMed PubMed Citation Articles by Rodenbaugh, D. W. Articles by Metzger, J. M.

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

¹Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; and ²Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida

Submitted 22 February 2007 ; accepted in final form 31 May 2007

The cytosolic Ca²⁺/Mg²⁺-binding protein -parvalbumin (-Parv) has been shown to accelerate cardiac relaxation; however, beyond an optimal concentration range, -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 /-Parv isoforms show divergence in amino acid primary structure (57% homology) and cation-binding affinities, with -Parv having an estimated 16% greater Mg²⁺ affinity and 200% greater Ca²⁺ affinity than -Parv. We tested the hypothesis that, at the same or lower estimated [Parv], mechanical relaxation rate would be more significantly accelerated by -Parv than by -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 - or -Parv adenoviral vectors. Upon Parv gene transfer, -Parv caused significantly faster relaxation than -Parv (P < 0.05), even though estimated [-Parv] was 10% of [-Parv]. This comparative analysis showing distinct functional outcomes raises the prospect of utilizing naturally occurring Parv variants to address disease-associated slowed cardiac relaxation.

gene transfer; mechanical relaxation