Cell Biochemistry and Biophysics

, Volume 40, Issue 2, pp 207–224 | Cite as

Membrane topology and membrane retention of the ryanodine receptor calcium release channel

Review Article


The ryanodine receptor (RyR) is a Ca2+ release channel located in the sarcoplasmic/endoplasmic reticulum (ER) membrane and plays a critical role in excitation-contraction coupling of skeletal and cardiac muscles. RyR normally exists in a tetrameric structure and contains two functional domains: a carboxyl-terminal hydrophobic domain that contains the conduction pore of the Ca2+ release channel, and a large amino-terminal domain that contains sites responsible for channel regulation. Recent studies involving mutagenesis and heterologous expression have helped unravel the structure-function relationship of RyR, including transmembrane topology and intracellular localization of the Ca2+-release channel. The carboxyl-terminal portion of RyR contains the putative transmembrane segments and is sufficient to form a functional Ca2+-release channel. The amino-terminal region of the protein contains sites responsible for regulation by endogenous modulators such as Ca2+ and Mg2+ and by exogenous ligands such as caffeine. The membrane topology of RyR appears to contain an even number (four or six) of transmembrane segments with a ion selectivity filter present within a region residing between the last two segments, similar to potassium channel, whose atomic structure was described recently. The transmembrane segments also contain sequences that are responsible for localization of RyR in the endoplasmic reticulum, and this sequence is highly conserved in IP3 receptors, which also function as Ca2+-release channels.

Index Entries

Calcium ryanodine endoplasmic reticulum caffeine 


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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Jianjie Ma
    • 1
  • Salim M. Hayek
    • 2
  • Manjunatha B. Bhat
    • 1
    • 2
  1. 1.Department of Physiology and BiophysicsUMDNJ-Robert Wood Johnson Medical SchoolPiscataway
  2. 2.The Cleveland Clinic FoundationCenter for Anesthesiology Research/FF40Cleveland

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