title: Toward a molecular understanding of the structure-function of ryanodine receptor Ca2+ release channels: perspectives from recombinant expression systems.
abstract: Identification of the genetic basis of human diseases linked to dysfunctional free calcium (Ca2+) signaling has triggered an explosion of interest in the functional characterization of the molecular components regulating intracellular Ca2+ homeostasis. There is a growing appreciation of the central role of intracellular ryanodine-sensitive Ca2+ release channel (RyR) regulation in skeletal and cardiac muscle pathologies, including malignant hyperthermia, heart failure, and sudden cardiac death. The use of cloned RyR isoforms and recombinant expression techniques has greatly facilitated the elucidation of the molecular basis of RyR Ca2+ release functionality. This review will focus on the recombinant techniques used in the functional characterization of recombinant RyR isoforms and the insights that these approaches have yielded in unraveling the mechanistic basis of RyR channel functionality.
authors.affiliation: Wales Heart Research Institute, Department of Cardiology, College of Medicine, Cardiff University, UK CF14 4XN. georgech@cf.ac.uk
authors.forename: Christopher H
authors.initials: CH
authors.lastname: George
authors.forename: Chang Cheng
authors.initials: CC
authors.lastname: Yin
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Lai
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium