title: Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart.
abstract: The roles of the Ca2+-mobilising messenger inositol 1,4,5-trisphosphate (InsP3) in heart are unclear, although many hormones activate InsP3 production in cardiomyocytes and some of their inotropic, chronotropic and arrhythmogenic effects may be due to Ca2+ release mediated by InsP3 receptors (InsP3Rs) [1-3]. In the present study, we examined the expression and subcellular localisation of InsP3R isoforms, and investigated their potential role in modulating excitation-contraction coupling (EC coupling). Western, PCR and InsP3-binding analysis indicated that both atrial and ventricular myocytes expressed mainly type II InsP3Rs, with approximately sixfold higher levels of InsP3Rs in atrial cells. Co-immunostaining of atrial myocytes with antibodies against type II ryanodine receptors (RyRs) and type II InsP3Rs revealed that the latter were arranged in the subsarcolemmal space where they largely co-localised with the junctional RyRs. Stimulation of quiescent or electrically paced atrial myocytes with a membrane-permeant InsP3 ester, which enters cells and directly activates InsP3Rs, caused the appearance of spontaneous Ca2+-release events. In addition, in paced cells, the InsP3 ester evoked an increase in the amplitudes of action potential-evoked Ca2+ transients. These data indicate that atrial cardiomyocytes express functional InsP3Rs, and that these channels could modulate EC coupling.
authors.affiliation: Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK.
authors.forename: P
authors.initials: P
authors.lastname: Lipp
authors.forename: M
authors.initials: M
authors.lastname: Laine
authors.forename: S C
authors.initials: SC
authors.lastname: Tovey
authors.forename: K M
authors.initials: KM
authors.lastname: Burrell
authors.forename: M J
authors.initials: MJ
authors.lastname: Berridge
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: M D
authors.initials: MD
authors.lastname: Bootman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear