title: Interaction of ions with the luminal sides of wild-type and mutated skeletal muscle ryanodine receptors.
abstract: Ryanodine receptors (RyRs) are the largest known ion channels, and are of central importance for the release of Ca(2+) from the sarco/endoplasmic reticulum (SR/ER) in a variety of cells. In cardiac and skeletal muscle cells, contraction is triggered by the release of Ca(2+) into the cytoplasm and thus depends crucially on correct RyR function. In this work, in silico mutants of the RyR pore were generated and MD simulations were conducted to examine the impact of the mutations on the Ca(2+) distribution. The Ca(2+) distribution pattern on the luminal side of the RyR was most affected by G4898R, D4899Q, E4900Q, R4913E, and D4917A mutations. MD simulations with our wild-type model and various ion species showed a preference for Ca(2+) over other cations at the luminal pore entrance. This Ca(2+)-accumulating characteristic of the luminal RyR side may be essential to the conductance properties of the channel.
authors.affiliation: Medical Biophysics Group, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120, Heidelberg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Schilling
authors.affiliation: Medical Biophysics Group, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120, Heidelberg, Germany.
authors.forename: Rainer H A
authors.initials: RH
authors.lastname: Fink
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, 155, Li-Non St., Sec. 2, Taipei, 112, Taiwan. wfischer@ym.edu.tw.|Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, 112, Taiwan. wfischer@ym.edu.tw.
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D019943:Amino Acid Substitution; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D020125:Mutation, Missense; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium
keywords: Calcium; Ion channel; Ion dynamics; Molecular dynamics simulations; RyR1