title: Alterations of cardiac beta-adrenoceptor mechanisms due to calcium depletion and repletion.
abstract: In order to understand the modification of beta-adrenoceptor linked signal transduction by changes in the intracellular Ca2+, we examined the status of beta-adrenoceptors (beta-ARs), G-proteins and adenylyl cyclase (AC) in Ca2+-deficiency and Ca2+-overload by perfusing the isolated rat heart with Ca2+-free medium for 5 min and Ca2+-containing medium for 5 min following Ca2+-free perfusion, respectively. Ca2+-depletion caused not only an increase in basal, isoproterenol-, Gpp(NH)p-, NaF- and forskolin-stimulated AC activities but also produced an increase in the beta1-AR affinity and density as well as up-regulation of G(s)-protein function and uncoupling of G(i)-protein to AC. Ca2+-repletion for 5 min following 5 min Ca2+-free perfusion reversed the increased AC activities to varying degrees. The beta1-AR affinity was further increased upon Ca2+-repletion whereas its density was decreased. Ca2+-repletion also decreased protein content for AC and beta-AR kinase but augmented the changes in G(s)- and G(i)-protein functions. Although low Na+ medium perfusion during Ca2+-depletion prevented the changes in G-proteins during both Ca2+-depletion and Ca2+-repletion periods, the increased beta1-AR affinity and density as well as changes in AC activities due to Ca2+-depletion were not affected while alterations due to Ca2+-repletion were fully prevented. These results suggest that changes in Ca2+-homeostasis may represent a mechanism for alterations in the beta-adrenergic signal transduction pathway in the heart under pathological conditions.
authors.affiliation: Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Wang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Vijayan
authors.initials: V
authors.lastname: Elimban
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D037342:Pertussis Toxin / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D011943:Receptors, Adrenergic, beta; D002772:Cholera Toxin; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium