title: Expression of slow skeletal troponin I in hearts of phospholamban knockout mice alters the relaxant effect of beta-adrenergic stimulation.
abstract: Beta-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 beta-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 beta-adrenergic stimulation.
authors: Department of Medicine, Section of Cardiology, University of Illinois at Chicago, Chicago, Ill 60612-7323, USA. bwolska@uic.edu
authors: Beata M
authors: BM
authors: Wolska
authors: Grace M
authors: GM
authors: Arteaga
authors: James R
authors: JR
authors: Peña
authors: Grzegorz
authors: G
authors: Nowak
authors: Ronald M
authors: RM
authors: Phillips
authors: Shalini
authors: S
authors: Sahai
authors: Pieter P
authors: PP
authors: de Tombe
authors: Anne F
authors: AF
authors: Martin
authors: Evangelia G
authors: EG
authors: Kranias
authors: R John
authors: RJ
authors: Solaro
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D046508:Culture Techniques; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D019210:Troponin I / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D000099211:Phospholamban
chemical_list: D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D007545:Isoproterenol; D019210:Troponin I; D014665:Vasodilator Agents; D000099211:Phospholamban