title: Troponin I converts the skeletal muscle ryanodine receptor into a rectifying calcium release channel.
abstract: The goal of our present studies has been to find novel ryanodine receptor (RyR1) interacting polypeptides that modulate the channel activity from the luminal side of RyR1. Using K(+) as charge carrier for recording of single channel events here we demonstrate a very unexpected observation that troponin I substantially alters RyR's gating behavior, and that RyR1 in association with troponin I becomes a rectifying Ca(2+) release channel. Troponin I rapidly locks the RyR1 in a non-conducting state only at a negative holding potential, and only when applied to the luminal side; switching to a positive holding potential results in the channel returning to its original activity, immediately. A hypothesis is proposed to account for how an intraluminally located, positively charged molecule might function as a RyR1 regulator under physiological conditions.
authors.affiliation: Institut für Physiologische Chemie, Ruhr Universität, D-44780, Bochum, Germany. magdolna.varsanyi@ruhr-uni-bochum.de
authors.forename: Magdolna
authors.initials: M
authors.lastname: Varsányi
authors.forename: Sándor
authors.initials: S
authors.lastname: Sárközi
authors.forename: Csaba
authors.initials: C
authors.lastname: Szegedi
authors.forename: Anke
authors.initials: A
authors.lastname: Herzog
authors.forename: István
authors.initials: I
authors.lastname: Jóna
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000737:chemistry*; D011188:Potassium / Q000378:metabolism; D021122:Protein Subunits; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000737:chemistry; D019210:Troponin I / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
chemical_list: D015220:Calcium Channels; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D021122:Protein Subunits; D019837:Ryanodine Receptor Calcium Release Channel; D019210:Troponin I; D011188:Potassium