Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016962.36404.04
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Submitted on October 26, 2001
Revised on March 18, 2002
Accepted on March 19, 2002
Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of ß-Adrenergic Stimulation
Beata M. Wolska *;
From the Department of Medicine, Section of Cardiology (B.M.W., J.R.P., G.N., P.P.d.T.), Department of Physiology and Biophysics (B.M.W., G.M.A., R.M.P., P.P.d.T., A.F.M., R.J.S.), Department of Pediatrics (G.M.A., S.S.), and Program in Cardiovascular Sciences (B.M.W., G.M.A., R.M.P., P.P.d.T., A.F.M., R.J.S.), University of Illinois at Chicago, Chicago, Ill; and Department of Pharmacology and Cell Biology (E.G.K.), University of Cincinnati, Cincinnati, Ohio.
* To whom correspondence should be addressed. E-mail: bwolska{at}uic.edu.
ß-Adrenergic stimulation of the heart results in an enhanced relaxation rate in association with phosphorylation of both cardiac troponin I (cTnI) and phospholamban (PLB). We studied new lines of mice generated by crossbreeding mice that express slow skeletal troponin I (ssTnI) with PLB knockout (PLBKO) mice. This crossbreeding resulted in the generation of PLB/cTnI, PLB/ssTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. Perfusion with isoproterenol (ISO) significantly increased the peak amplitude of fura-2 ratio in PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI groups of mice. However, in the presence of ISO, there were no differences in the peak amplitude of fura-2 ratio among cells isolated from hearts of PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. In cells from PLB/cTnI mice, the extent of shortening was increased and the time of relaxation was significantly decreased during ß-adrenergic stimulation. In PLBKO/cTnI cells, stimulation with ISO resulted in an increased extent of shortening and no change in time of relaxation. However, stimulation with ISO in cells isolated from PLBKO/ssTnI mice not only significantly increased the extent of cell shortening but also increased the time of relaxation. We also determined the kinetics of relaxation of papillary muscles isolated from all four groups of animals in the presence and absence of ISO. Perfusion with ISO increased the rate of relaxation only in PLB/cTnI, PLB/ssTnI, and PLBKO/cTnI muscles. During ISO stimulation, the time of relaxation was unchanged in PLBKO/ssTnI muscles. Our data directly demonstrate that phosphorylation of both PLB and cTnI contributes to increased rate of relaxation during ß-adrenergic stimulation.
Key words: troponin I • phospholamban • ß-adrenergic stimulation • relaxation
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