{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:07:53Z","timestamp":1785564473248,"version":"3.56.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>Relaxation abnormalities are prevalent in heart failure and contribute to clinical outcomes. Disruption of Ca<jats:sup>2+<\/jats:sup>homeostasis in heart failure delays relaxation by prolonging the intracellular Ca<jats:sup>2+<\/jats:sup>transient. We sought to speed cardiac relaxation in vivo by cardiac-directed transgene expression of parvalbumin (Parv), a cytosolic Ca<jats:sup>2+<\/jats:sup>buffer normally expressed in fast-twitch skeletal muscle. A key feature of Parv's function resides in its Ca<jats:sup>2+<\/jats:sup>\/Mg<jats:sup>2+<\/jats:sup>binding affinities that account for delayed Ca<jats:sup>2+<\/jats:sup>buffering in response to the intracellular Ca<jats:sup>2+<\/jats:sup>transient. Cardiac Parv expression decreased sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>content without otherwise altering intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis. At high physiological mouse heart rates in vivo, Parv modestly accelerated relaxation without affecting cardiac morphology or systolic function. Ex vivo pacing of the isolated heart revealed a marked heart rate dependence of Parv's delayed Ca<jats:sup>2+<\/jats:sup>buffering effects on myocardial performance. As the pacing frequency was lowered (7 to 2.5 Hz), the relaxation rates increased in Parv hearts. However, as pacing rates approached the dynamic range in humans, Parv hearts demonstrated decreased contractility, consistent with Parv buffering systolic Ca<jats:sup>2+<\/jats:sup>. Mathematical modeling and in vitro studies provide the underlying mechanism responsible for the frequency-dependent fractional Ca<jats:sup>2+<\/jats:sup>buffering action of Parv. Future studies directed toward refining the dose and frequency-response relationships of Parv in the heart or engineering novel Parv-based Ca<jats:sup>2+<\/jats:sup>buffers with modified Mg<jats:sup>2+<\/jats:sup>and Ca<jats:sup>2+<\/jats:sup>affinities to limit systolic Ca<jats:sup>2+<\/jats:sup>buffering may hold promise for the development of new therapies to remediate relaxation abnormalities in heart failure.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00302.2007","type":"journal-article","created":{"date-parts":[[2008,3,12]],"date-time":"2008-03-12T03:25:13Z","timestamp":1205292313000},"page":"312-322","source":"Crossref","is-referenced-by-count":10,"title":["Cardiac-directed parvalbumin transgene expression in mice shows marked heart rate dependence of delayed Ca<sup>2+<\/sup>buffering action"],"prefix":"10.1152","volume":"33","author":[{"given":"Sharlene M.","family":"Day","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical 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