- Title
- Regulation of the RyR channel gating by Ca²⁺ and Mg²⁺
- Creator
- Laver, Derek R.
- Relation
- Biophysical Reviews Vol. 10, Issue 4, p. 1087-1095
- Publisher Link
- http://dx.doi.org/10.1007/s12551-018-0433-4
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2018
- Description
- Ryanodine receptors (RyRs) are the Ca2+ release channels in the sarcoplasmic reticulum in striated muscle which play an important role in excitation-contraction coupling and cardiac pacemaking. Single channel recordings have revealed a wealth of information about ligand regulation of RyRs from mammalian skeletal and cardiac muscle (RyR1 and RyR2, respectively). RyR subunit has a Ca2+ activation site located in the luminal and cytoplasmic domains of the RyR. These sites synergistically feed into a common gating mechanism for channel activation by luminal and cytoplasmic Ca2+. RyRs also possess two inhibitory sites in their cytoplasmic domains with Ca2+ affinities of the order of 1 µM and 1 mM. Magnesium competes with Ca2+ at these sites to inhibit RyRs and this plays an important role in modulating their Ca2+-dependent activity in muscle. This review focuses on how these sites lead to RyR modulation by Ca2+ and Mg2+ and how these mechanisms control Ca2+ release in excitation-contraction coupling and cardiac pacemaking.
- Subject
- ryanodine receptor; RyR1; RyR2; excitation-contraction coupling; cardiac pacemaking; Ca²⁺ activation; Mg²⁺ inhibition; Ca²⁺ release channels
- Identifier
- http://hdl.handle.net/1959.13/1391675
- Identifier
- uon:33272
- Identifier
- ISSN:1867-2450
- Language
- eng
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