%0 Journal Article %1 Lave_2005_359 %A Laver, Derek R %D 2005 %J Eur. Biophys. J. %K Adenosine Allosteric Animals; Bilayers; Binding Biophysics; Calcium Calcium; Cations; Channel; Channels; Cytoplasm; Cytosol; Dose-Response Drug; Ions; Isoforms; Lipid Magnesium; Membrane Muscle, Potentials; Protein Receptor Relationship, Release Reticulum; Ryanodine Ryanodine; Sarcoplasmic Site; Sites; Skeletal; Temperature Triphosphate; %N 5 %P 359--368 %R 10.1007/s00249-005-0483-y %T Coupled calcium release channels and their regulation by luminal and cytosolic ions. %U http://dx.doi.org/10.1007/s00249-005-0483-y %V 34 %X Contraction in skeletal and cardiac muscle occurs when Ca$^2+$ is released from the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR) Ca$^2+$ release channels. Several isoforms of the RyR exist throughout the animal kingdom, which are modulated by ATP, Ca$^2+$ and Mg$^2+$ in the cytoplasm and by Ca$^2+$ in the lumen of the SR. This review brings to light recent findings on their mechanisms of action in the mammalian isoforms RyR-1 and RyR-2 with an emphasis on RyR-1 from skeletal muscle. Cytoplasmic Mg$^2+$ is a potent RyR antagonist that binds to two classes of cytoplasmic site, identified as low-affinity, non-specific inhibition sites and high-affinity Ca$^2+$ activation sites (A-sites). Mg$^2+$ inhibition at the A-sites is very sensitive to the cytoplasmic and luminal milieu. Cytoplasmic Ca$^2+$, Mg$^2+$ and monovalent cations compete for the A-sites. In isolated RyRs, luminal Ca$^2+$ alters the Mg$^2+$ affinity of the A-site by an allosteric mechanism mediated by luminal sites. However, in close-packed RyR arrays luminal Ca$^2+$ can also compete with cytoplasmic ions for the A-site. Activation of RyRs by luminal Ca$^2+$ has been attributed to either Ca$^2+$ feedthrough to A-sites or to Ca$^2+$ regulatory sites on the luminal side of the RyR. As yet there is no consensus on just how luminal Ca$^2+$ alters RyR activation. Recent evidence indicates that both mechanisms operate and are likely to be important. Allosteric regulation of A-site Mg$^2+$ affinity could trigger Ca$^2+$ release, which is reinforced by Ca$^2+$ feedthrough.

@article{Lave_2005_359, abstract = {Contraction in skeletal and cardiac muscle occurs when {C}a$^{2+}$ is released from the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR) {C}a$^{2+}$ release channels. Several isoforms of the RyR exist throughout the animal kingdom, which are modulated by ATP, {C}a$^{2+}$ and {M}g$^{2+}$ in the cytoplasm and by {C}a$^{2+}$ in the lumen of the SR. This review brings to light recent findings on their mechanisms of action in the mammalian isoforms RyR-1 and RyR-2 with an emphasis on RyR-1 from skeletal muscle. Cytoplasmic {M}g$^{2+}$ is a potent RyR antagonist that binds to two classes of cytoplasmic site, identified as low-affinity, non-specific inhibition sites and high-affinity {C}a$^{2+}$ activation sites (A-sites). {M}g$^{2+}$ inhibition at the A-sites is very sensitive to the cytoplasmic and luminal milieu. Cytoplasmic {C}a$^{2+}$, {M}g$^{2+}$ and monovalent cations compete for the A-sites. In isolated RyRs, luminal {C}a$^{2+}$ alters the {M}g$^{2+}$ affinity of the A-site by an allosteric mechanism mediated by luminal sites. However, in close-packed RyR arrays luminal {C}a$^{2+}$ can also compete with cytoplasmic ions for the A-site. Activation of RyRs by luminal {C}a$^{2+}$ has been attributed to either {C}a$^{2+}$ feedthrough to A-sites or to {C}a$^{2+}$ regulatory sites on the luminal side of the RyR. As yet there is no consensus on just how luminal {C}a$^{2+}$ alters RyR activation. Recent evidence indicates that both mechanisms operate and are likely to be important. Allosteric regulation of A-site {M}g$^{2+}$ affinity could trigger {C}a$^{2+}$ release, which is reinforced by {C}a$^{2+}$ feedthrough.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Laver, Derek R}, biburl = {https://www.bibsonomy.org/bibtex/21237d27c489aa6f632863f7577e92884/hake}, description = {The whole bibliography file I use.}, doi = {10.1007/s00249-005-0483-y}, institution = {School of Biomedical Sciences, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308, Australia. derek.laver@newcastle.edu.au}, interhash = {36be7284a2effedc0ba88a82b51c434f}, intrahash = {1237d27c489aa6f632863f7577e92884}, journal = {Eur. Biophys. J.}, keywords = {Adenosine Allosteric Animals; Bilayers; Binding Biophysics; Calcium Calcium; Cations; Channel; Channels; Cytoplasm; Cytosol; Dose-Response Drug; Ions; Isoforms; Lipid Magnesium; Membrane Muscle, Potentials; Protein Receptor Relationship, Release Reticulum; Ryanodine Ryanodine; Sarcoplasmic Site; Sites; Skeletal; Temperature Triphosphate;}, month = Jul, number = 5, pages = {359--368}, pmid = {15915341}, timestamp = {2009-06-03T11:21:19.000+0200}, title = {Coupled calcium release channels and their regulation by luminal and cytosolic ions.}, url = {http://dx.doi.org/10.1007/s00249-005-0483-y}, volume = 34, year = 2005 }