{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/17891"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/17891","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"The Function Of Sarcoplasmic Reticulum In The Aged Rat Heart","abstract":"The purpose of this project was to study the effect of aging on the regulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} by cardiac sarcoplasmic reticulum (SR) and its potential contribution to the age-related alterations in myocardial contractile performance in Fischer 344 rats.;In cardiac membranes enriched in SR (MSR) and its light (LSR) and heavy (HSR) subfractions fractionated by a sucrose density gradient, the rate of ATP-supported and oxalate-facilitated Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake was significantly reduced (24-50%) in the aged (26-30 months old) compared with that of the adult rats (6-8 months old). With aging, the Ca{dollar}sp{lcub}2+{rcub}{dollar}-stimulated phosphoenzyme of the Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps was reduced in MSR, LSR (25% and 33% respectively) but not in HSR; the Ca{dollar}sp{lcub}2+{rcub}{dollar}-ATPase activity was significantly reduced in LSR only (35%). The pump turnover rates were not significantly altered with aging in MSR, LSR and HSR. The coupling ratio was reduced by 26-46% in MSR but was not markedly altered in LSR and HSR. The density of the Ca{dollar}sp{lcub}2+{rcub}{dollar} release channels and the rate of Ca{dollar}sp{lcub}2+{rcub}{dollar}-induced Ca{dollar}sp{lcub}2+{rcub}{dollar} release from HSR were not altered with aging. Thus the age-related decline in the active Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by SR membranes is likely due to a reduction in the density of active Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps and/or in the efficiency of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps. The Ca{dollar}sp{lcub}2+{rcub}{dollar} release function of SR is not altered with aging. The reduced rate of SR Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake may contribute to the prolonged myocardial relaxation in aging.;In the intact perfused heart, {dollar}beta{dollar}-adrenergic agonist isoproterenol-stimulated peak inotropic and lusitropic responses were significantly reduced with aging. Under similar conditions, isoproterenol (0.1 {dollar}mu{dollar}M)-stimulated phosphorylation of phospholamban in situ was significantly compromised with aging (38%), which was associated with an age-related reduction in the isoproterenol-stimulated accumulation of tissue cyclic AMP (18%). However, the cyclic AMP-dependent phosphorylation of phospholamban and its stimulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake in vitro were not reduced with aging. It is concluded that the age-related reduction in the phosphorylation of phospholamban, which is in part due to an age-related decline in cyclic AMP accumulation, contributes to the diminished myocardial contractile responses to {dollar}beta{dollar}-adrenergic stimulation in aging.","abstract_html":"The purpose of this project was to study the effect of aging on the regulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} by cardiac sarcoplasmic reticulum (SR) and its potential contribution to the age-related alterations in myocardial contractile performance in Fischer 344 rats.;In cardiac membranes enriched in SR (MSR) and its light (LSR) and heavy (HSR) subfractions fractionated by a sucrose density gradient, the rate of ATP-supported and oxalate-facilitated Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake was significantly reduced (24-50%) in the aged (26-30 months old) compared with that of the adult rats (6-8 months old). With aging, the Ca{dollar}sp{lcub}2+{rcub}{dollar}-stimulated phosphoenzyme of the Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps was reduced in MSR, LSR (25% and 33% respectively) but not in HSR; the Ca{dollar}sp{lcub}2+{rcub}{dollar}-ATPase activity was significantly reduced in LSR only (35%). The pump turnover rates were not significantly altered with aging in MSR, LSR and HSR. The coupling ratio was reduced by 26-46% in MSR but was not markedly altered in LSR and HSR. The density of the Ca{dollar}sp{lcub}2+{rcub}{dollar} release channels and the rate of Ca{dollar}sp{lcub}2+{rcub}{dollar}-induced Ca{dollar}sp{lcub}2+{rcub}{dollar} release from HSR were not altered with aging. Thus the age-related decline in the active Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by SR membranes is likely due to a reduction in the density of active Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps and/or in the efficiency of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps. The Ca{dollar}sp{lcub}2+{rcub}{dollar} release function of SR is not altered with aging. The reduced rate of SR Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake may contribute to the prolonged myocardial relaxation in aging.;In the intact perfused heart, {dollar}beta{dollar}-adrenergic agonist isoproterenol-stimulated peak inotropic and lusitropic responses were significantly reduced with aging. Under similar conditions, isoproterenol (0.1 {dollar}mu{dollar}M)-stimulated phosphorylation of phospholamban in situ was significantly compromised with aging (38%), which was associated with an age-related reduction in the isoproterenol-stimulated accumulation of tissue cyclic AMP (18%). However, the cyclic AMP-dependent phosphorylation of phospholamban and its stimulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake in vitro were not reduced with aging. It is concluded that the age-related reduction in the phosphorylation of phospholamban, which is in part due to an age-related decline in cyclic AMP accumulation, contributes to the diminished myocardial contractile responses to {dollar}beta{dollar}-adrenergic stimulation in aging.","abstract_has_math":false,"creators":["Jiang, Ming Tao"],"institution":null,"degree_name":"Ph D","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1995,"date_issued":"1995-01-01","date_published":"1995-01-01","updated_at":"2026-07-27T21:56:03Z","subjects":["Biology","Animal Physiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/17891","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Jiang, Ming Tao"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-25T18:46:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-25T18:46:01Z"]},{"key":"dc:date.issued","label":"Date","values":["1995-01-01"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph D"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Animal Physiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/17891"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The purpose of this project was to study the effect of aging on the regulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} by cardiac sarcoplasmic reticulum (SR) and its potential contribution to the age-related alterations in myocardial contractile performance in Fischer 344 rats.;In cardiac membranes enriched in SR (MSR) and its light (LSR) and heavy (HSR) subfractions fractionated by a sucrose density gradient, the rate of ATP-supported and oxalate-facilitated Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake was significantly reduced (24-50%) in the aged (26-30 months old) compared with that of the adult rats (6-8 months old). With aging, the Ca{dollar}sp{lcub}2+{rcub}{dollar}-stimulated phosphoenzyme of the Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps was reduced in MSR, LSR (25% and 33% respectively) but not in HSR; the Ca{dollar}sp{lcub}2+{rcub}{dollar}-ATPase activity was significantly reduced in LSR only (35%). The pump turnover rates were not significantly altered with aging in MSR, LSR and HSR. The coupling ratio was reduced by 26-46% in MSR but was not markedly altered in LSR and HSR. The density of the Ca{dollar}sp{lcub}2+{rcub}{dollar} release channels and the rate of Ca{dollar}sp{lcub}2+{rcub}{dollar}-induced Ca{dollar}sp{lcub}2+{rcub}{dollar} release from HSR were not altered with aging. Thus the age-related decline in the active Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by SR membranes is likely due to a reduction in the density of active Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps and/or in the efficiency of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps. The Ca{dollar}sp{lcub}2+{rcub}{dollar} release function of SR is not altered with aging. The reduced rate of SR Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake may contribute to the prolonged myocardial relaxation in aging.;In the intact perfused heart, {dollar}beta{dollar}-adrenergic agonist isoproterenol-stimulated peak inotropic and lusitropic responses were significantly reduced with aging. Under similar conditions, isoproterenol (0.1 {dollar}mu{dollar}M)-stimulated phosphorylation of phospholamban in situ was significantly compromised with aging (38%), which was associated with an age-related reduction in the isoproterenol-stimulated accumulation of tissue cyclic AMP (18%). However, the cyclic AMP-dependent phosphorylation of phospholamban and its stimulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake in vitro were not reduced with aging. It is concluded that the age-related reduction in the phosphorylation of phospholamban, which is in part due to an age-related decline in cyclic AMP accumulation, contributes to the diminished myocardial contractile responses to {dollar}beta{dollar}-adrenergic stimulation in aging."]},{"key":"dc:title","label":"Title","values":["The Function Of Sarcoplasmic Reticulum In The Aged Rat Heart"]}]}],"canonical_facts":{"dc:creator":["Jiang, Ming Tao"],"dc:date.accessioned":["2025-06-25T18:46:01Z"],"dc:date.available":["2025-06-25T18:46:01Z"],"dc:date.issued":["1995-01-01"],"dc:description.abstract":["The purpose of this project was to study the effect of aging on the regulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} by cardiac sarcoplasmic reticulum (SR) and its potential contribution to the age-related alterations in myocardial contractile performance in Fischer 344 rats.;In cardiac membranes enriched in SR (MSR) and its light (LSR) and heavy (HSR) subfractions fractionated by a sucrose density gradient, the rate of ATP-supported and oxalate-facilitated Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake was significantly reduced (24-50%) in the aged (26-30 months old) compared with that of the adult rats (6-8 months old). With aging, the Ca{dollar}sp{lcub}2+{rcub}{dollar}-stimulated phosphoenzyme of the Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps was reduced in MSR, LSR (25% and 33% respectively) but not in HSR; the Ca{dollar}sp{lcub}2+{rcub}{dollar}-ATPase activity was significantly reduced in LSR only (35%). The pump turnover rates were not significantly altered with aging in MSR, LSR and HSR. The coupling ratio was reduced by 26-46% in MSR but was not markedly altered in LSR and HSR. The density of the Ca{dollar}sp{lcub}2+{rcub}{dollar} release channels and the rate of Ca{dollar}sp{lcub}2+{rcub}{dollar}-induced Ca{dollar}sp{lcub}2+{rcub}{dollar} release from HSR were not altered with aging. Thus the age-related decline in the active Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by SR membranes is likely due to a reduction in the density of active Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps and/or in the efficiency of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake by Ca{dollar}sp{lcub}2+{rcub}{dollar} pumps. The Ca{dollar}sp{lcub}2+{rcub}{dollar} release function of SR is not altered with aging. The reduced rate of SR Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake may contribute to the prolonged myocardial relaxation in aging.;In the intact perfused heart, {dollar}beta{dollar}-adrenergic agonist isoproterenol-stimulated peak inotropic and lusitropic responses were significantly reduced with aging. Under similar conditions, isoproterenol (0.1 {dollar}mu{dollar}M)-stimulated phosphorylation of phospholamban in situ was significantly compromised with aging (38%), which was associated with an age-related reduction in the isoproterenol-stimulated accumulation of tissue cyclic AMP (18%). However, the cyclic AMP-dependent phosphorylation of phospholamban and its stimulation of Ca{dollar}sp{lcub}2+{rcub}{dollar} uptake in vitro were not reduced with aging. It is concluded that the age-related reduction in the phosphorylation of phospholamban, which is in part due to an age-related decline in cyclic AMP accumulation, contributes to the diminished myocardial contractile responses to {dollar}beta{dollar}-adrenergic stimulation in aging."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/17891"],"dc:subject":["Biology","Animal Physiology"],"dc:title":["The Function Of Sarcoplasmic Reticulum In The Aged Rat Heart"],"dc:type":["thesis"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:56:03Z"}