title: Impact of RyR2 potentiation on myocardial function.
abstract: This perspective attempts to shed light on an old and not yet solved controversy in cardiac physiology, i.e., the impact of increasing ryanodine receptor (RyR)2 open probability on myocardial function. Based on an already proven myocyte model, it was shown that increasing RyR2 open probability results in a purely short-lived increase in Ca2+transient amplitude, and, therefore, it does not increase cardiac contractility. However, potentiation of RyR2 activity permanently enhances fractional Ca2+release, shifting the intracellular Ca2+transient versus sarcoplasmic reticulum (SR) Ca2+content curve to a new state of higher efficiency. This would allow the heart to maintain a given contractility despite a decrease in SR Ca2+content, to enhance contractility if SR Ca2+content is simultaneously preserved or to successfully counteract the effects of a negative inotropic intervention.NEW & NOTEWORTHYIncreasing ryanodine receptor (RyR)2 open probability does not increase cardiac contractility. However, RyR2 potentiation shifts the intracellular Ca2+transient-sarcoplasmic reticulum (SR) Ca2+content relationship toward an enhanced efficiency state, which may contribute to a positive inotropic effect, preserve contractility despite decreased SR Ca2+content, or successfully counteract the effects of a negative inotropic action.
authors.affiliation: Instituto de Medicina Translacional, Transplante y Bioingeniería, Universidad Favaloro, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; and.
authors.forename: E
authors.initials: E
authors.lastname: Lascano
authors.affiliation: Instituto de Medicina Translacional, Transplante y Bioingeniería, Universidad Favaloro, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; and.
authors.forename: J
authors.initials: J
authors.lastname: Negroni
authors.affiliation: Centro de Investigaciones Cardiovasculares, CCT-La Plata-CONICET, Facultad de Cs. Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Vila Petroff
authors.affiliation: Centro de Investigaciones Cardiovasculares, CCT-La Plata-CONICET, Facultad de Cs. Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina aliciamattiazzi@gmail.com ramattia@med.unlp.edu.ar.
authors.forename: A
authors.initials: A
authors.lastname: Mattiazzi
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel
keywords: contractility; heart; open probability; ryanodine receptor