title: Role of inositol 1,4,5-trisphosphate in the regulation of ventricular Ca(2+) signaling in intact mouse heart.
abstract: Inositol 1,4,5-trisphosphate (InsP(3)R)-mediated Ca(2+) signaling is a major pathway regulating multiple cellular functions in excitable and non-excitable cells. Although InsP(3)-mediated Ca(2+) signaling has been extensively described, its influence on ventricular myocardium activity has not been addressed in contracting hearts at the whole-organ level. In this work, InsP(3)-sensitive intracellular Ca(2+) signals were studied in intact hearts using laser scanning confocal microscopy and pulsed local-field fluorescence microscopy. Intracellular [InsP(3)] was rapidly increased by UV flash photolysis of membrane-permeant caged InsP(3). Our results indicate that the basal [Ca(2+)] increased after the flash photolysis of caged InsP(3) without affecting the action potential (AP)-induced Ca(2+) transients. The amplitude of the basal [Ca(2+)] elevation depended on the intracellular [InsP(3)] reached after the UV flash. Pretreatment with ryanodine failed to abolish the InsP(3)-induced Ca(2+) release (IICR), indicating that this response was not mediated by ryanodine receptors (RyR). Thapsigargin prevented Ca(2+) release from both RyR- and InsP(3)R-containing Ca(2+) stores, suggesting that these pools have similar Ca(2+) reuptake mechanisms. These results were reproduced in acutely isolated cells where photorelease of InsP(3) was able to induce changes in endothelial cells but not in AP-induced transients from cardiomyocytes. Taken together, these results suggest that IICR does not directly regulate cardiac excitation-contraction coupling. To our knowledge, this is the first demonstration of IICR in intact hearts. Consequently, our work provides a reference framework of the spatiotemporal attributes of the IICR under physiological conditions.
authors.affiliation: School of Engineering, University of California Merced, Merced, CA 95344, USA.
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Escobar
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Perez
authors.forename: Mariano E
authors.initials: ME
authors.lastname: Reyes
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Lucero
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kornyeyev
authors.forename: Rafael
authors.initials: R
authors.lastname: Mejía-Alvarez
authors.forename: Josefina
authors.initials: J
authors.lastname: Ramos-Franco
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D011485:Protein Binding; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium