title: Flux regulation of cardiac ryanodine receptor channels.
abstract: The cardiac type 2 ryanodine receptor (RYR2) is activated by Ca2+-induced Ca2+ release (CICR). The inherent positive feedback of CICR is well controlled in cells, but the nature of this control is debated. Here, we explore how the Ca2+ flux (lumen-to-cytosol) carried by an open RYR2 channel influences its own cytosolic Ca2+ regulatory sites as well as those on a neighboring channel. Both flux-dependent activation and inhibition of single channels were detected when there were super-physiological Ca2+ fluxes (>3 pA). Single-channel results indicate a pore inhibition site distance of 1.2 +/- 0.16 nm and that the activation site on an open channel is shielded/protected from its own flux. Our results indicate that the Ca2+ flux mediated by an open RYR2 channel in cells (approximately 0.5 pA) is too small to substantially regulate (activate or inhibit) the channel carrying it, even though it is sufficient to activate a neighboring RYR2 channel.
authors.affiliation: Department of Molecular Physiology and Biophysics, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Maura
authors.initials: M
authors.lastname: Porta
authors.forename: Jia
authors.initials: J
authors.lastname: Qin
authors.forename: Jorge
authors.initials: J
authors.lastname: Ramos
authors.forename: Alma
authors.initials: A
authors.lastname: Nani
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Shannon
authors.forename: Michael
authors.initials: M
authors.lastname: Fill
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D025461:Feedback, Physiological / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium