title: Role of SERCA and the sarcoplasmic reticulum calcium content on calcium waves propagation in rat ventricular myocytes.
abstract: In Ca(2+)-overloaded ventricular myocytes, SERCA is crucial to steadily achieve the critical sarcoplasmic reticulum (SR) Ca(2+) level to trigger and sustain Ca(2+) waves, that propagate at constant rate (ʋwave). High luminal Ca(2+) sensitizes RyR2, thereby increasing Ca(2+) sparks frequency, and the larger RyR2-mediated SR Ca(2+) flux (dF/dt) sequentially activates adjacent RyR2 clusters. Recently, it was proposed that rapid SERCA Ca(2+) reuptake, ahead of the wave front, further sensitizes RyR2, increasing ʋwave. Nevertheless, this is controversial because rapid cytosolic Ca(2+) removal could instead impair RyR2 activation. We assessed whether rapid SR Ca(2+) uptake enhances ʋwave by changing SERCA activity (ҡDecay) over a large range (∼175%). We used normal (Ctrl) and hyperthyroid rat (HT; reduced phospholamban by ∼80%) myocytes treated with thapsigargin or isoproterenol (ISO). We found that ʋwave and dF/dt had a non-linear dependency with ҡDecay, while Ca(2+) waves amplitude was largely unaffected. Furthermore, SR Ca(2+) also showed a non-linear dependency with ҡDecay, however, the relationships ʋwave vs. SR Ca(2+) and ʋwave vs. dF/dt were linear, suggesting that high steady state SR Ca(2+) determines ʋwave, while rapid SERCA Ca(2+) uptake does not. Finally, ISO did not increase ʋwave in HT cells, therefore, ISO-enhanced ʋwave in Ctrl depended on high SR Ca(2+).
authors.affiliation: Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., Monterrey, N.L., 64710, Mexico.
authors.forename: Ayleen
authors.initials: A
authors.lastname: Salazar-Cantú
authors.affiliation: Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., Monterrey, N.L., 64710, Mexico.
authors.forename: Perla
authors.initials: P
authors.lastname: Pérez-Treviño
authors.affiliation: Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., Monterrey, N.L., 64710, Mexico.
authors.forename: Dolores
authors.initials: D
authors.lastname: Montalvo-Parra
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-IPN sede Sur., D.F., 14330, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Balderas-Villalobos
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-IPN sede Sur., D.F., 14330, Mexico.
authors.forename: Norma L
authors.initials: NL
authors.lastname: Gómez-Víquez
authors.affiliation: Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., Monterrey, N.L., 64710, Mexico; Basic and Translational Research Center, Hospital Zambrano-Hellion, TecSalud, San Pedro Garza-García, N.L., 66278, Mexico.
authors.forename: Noemí
authors.initials: N
authors.lastname: García
authors.affiliation: Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., Monterrey, N.L., 64710, Mexico; Basic and Translational Research Center, Hospital Zambrano-Hellion, TecSalud, San Pedro Garza-García, N.L., 66278, Mexico. Electronic address: altamirano@itesm.mx.
authors.forename: Julio
authors.initials: J
authors.lastname: Altamirano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism; D007545:Isoproterenol / Q000737:chemistry; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D019284:Thapsigargin / Q000737:chemistry; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D007545:Isoproterenol; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin; D000099211:Phospholamban; C000612605:RyR2 protein, rat
keywords: Beta-adrenergic stimulation; Calcium waves; Calcium-triggered arrhythmias; Ryanodine receptors; SERCA; Ventricular myocytes