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1 Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: metzgerj{at}umich.edu.
Two genetic experimental approaches, de novo expression of parvalbumin (Parv) and over-expression of Serca2a, have been shown to increase relaxation rates in myocardial tissue. However, the relative effect of Parv and Serca2a on systolic function, 
-adrenergic responsiveness, and at varied pacing rates is still unknown. Here, we used gene transfer in isolated rat adult cardiac myocytes to gain a fuller understanding of Parv/Serca2a function. As demonstrated previously, when Parv is expressed in elevated concentration (>0.1 mM), the transduced myocytes showed a reduction in sarcomere shortening amplitude (Control: 129 ± 17 nm; Parv: 81 ± 8 nm; Serca2a: 149 ± 14 nm). At physiological temperature, Parv and Serca2a myocytes' shortening amplitude responses to the -adrenergic agonist isoproterenol (Iso) were not statistically different from control myocytes. However the Serca2a myocytes, which had a slightly elevated baseline and a slightly lower Iso-stimulated value, had a smaller increase in shortening compared to Parv or control myocytes (Control: 108 ± 14%, Parv: 169 ± 39%, Serca2a: 34 ± 12%; increase in sarcomere shortening amplitude). In another test set, Parv myocytes had the strongest early post rest potentiation among all groups studied (rest time: 2-10 s), and Serca2a myocytes were the least sensitive to variations in stimulation rhythm. To replicate deficient calcium removal observed in heart failure, we used 150 nM thapsigargin. Under these conditions, control myocytes exhibited slowed relaxation, while Parv myocytes retained their rapid kinetics, showing that Parv is still able to control relaxation even when Serca2a function is impaired.
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