title: Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic beta3-adrenoceptor deficiency.
abstract: This study investigated the influence of chronic beta(3)-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7). Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)-adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO. Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO. The conclusion is that depression of beta(3)-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.
authors.affiliation: Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Cologne, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ziskoven
authors.forename: Sabrina
authors.initials: S
authors.lastname: Grafweg
authors.forename: Birgit
authors.initials: B
authors.lastname: Bölck
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Wiesner
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Giacobino
authors.forename: W
authors.initials: W
authors.lastname: Bloch
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
authors.forename: Klara
authors.initials: K
authors.lastname: Brixius
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004452:Echocardiography; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D010766:Phosphorylation; D022702:Receptors, Adrenergic, beta-3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D019204:GTP-Binding Proteins; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506947:Atp2a2 protein, mouse