The ryanodine receptors (RyRs) are a family of Ca2+ channels that mediate the release of Ca2+ from intracellular Ca2+ storage organelles. Three RyR isoforms have been identified to date, RyR1, RyR2 and RyR3. The RyRs have a well-established role in the mechanism of excitation-contraction (EC) coupling in striated muscle contraction, and also have a role in secretion and synaptic transmission.
RyRs are expressed in the membrane of the sarcoplasmic (SR)/endoplasmic reticulum and are expressed in many tissues, with RyR1 and RyR2 being the predominant isoforms in skeletal and cardiac muscle respectively. RyR3 is expressed at low levels in striated muscle, however is abundant in the brain. RyR activity can either be voltage- or Ca2+-dependent, the latter being termed Ca2+-induced Ca2+ release (CICR). For example RyR1 is activated following membrane depolarization of skeletal muscle, whereas depolarization of cardiac muscle results in Ca2+ influx through L-type Ca2+ channels, which activates RyR2 by CICR. Incidentally the depolarization-induced activation of RyR1 channels in skeletal muscle is dependent on a physical interaction between RyR1 and L-type Ca2+ channels.
RyR activity can be modulated by multiple factors, including Ca2+, ATP and Mg2+, as well as various other proteins. Intracellular Ca2+ activates RyRs at low concentrations (1-10 μM), whereas high levels of Ca2+ (1-10 mM) have an inhibitory effect. Luminal SR Ca2+ concentration may also regulate RyR activity. ATP can also activate RyRs, whilst Mg2+ is a RyR channel inhibitor. The Ca2+ binding proteins, calmodulin and calsequesterin1 are thought to negatively regulate RyR activity, and FK506 binding proteins have been shown to stabilize RyRs in a closed conformation. Furthermore RyR phosphorylation is thought to induce channel opening, a mechanism that may cause SR calcium leak in the heart.
Dysregulation of RyR channel activity has been implicated in the pathogenesis of a number of debilitating muscular diseases. Point mutations of RyR1 have been associated with malignant hyperthermia, central core disease and atypical paralyses, whereas RyR2 mutations are associated with polymorphic ventricular tachycardia and right ventricular dysplasia. Interestingly RyR3 may be involved in Alzheimer's disease (AD), as increased expression of RyR3 in cortical neurons has been shown to be neuroprotective in a mouse model of AD.View all products for Ryanodine Receptors »
|Gene||Species||Gene Symbol||Gene Accession No.||Protein Accession No.|
|Ryanodine Receptor 1||Human||RYR1||NM_000540||P21817|
|Ryanodine Receptor 2||Human||RYR2||NM_001035||Q92736|
|Rat||Ryr2||NM_032078||NP_114467||View all Ryanodine Receptor Gene Data »|
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