ryanodine-sensitive calcium-release channel activity

Definition

Target type: molecularfunction

Enables transmembrane transfer of calcium ions from an intracellular store to the cytosol on induction by increased calcium concentration and is sensitive to the plant alkaloid ryanodine. [GOC:dph, GOC:tb, PMID:22822064]

Ryanodine-sensitive calcium-release channel activity represents a crucial molecular function in the regulation of intracellular calcium signaling, primarily in skeletal and cardiac muscle cells. These channels, also known as RyR receptors, are large transmembrane proteins located in the sarcoplasmic reticulum (SR), a specialized endoplasmic reticulum in muscle cells. They act as gated pores that control the release of calcium ions (Ca2+) from the SR into the cytoplasm, triggering muscle contraction.

The molecular mechanism of RyR-mediated calcium release involves a complex interplay of factors:

1. **Activation:** RyR channels are activated by a rise in cytoplasmic Ca2+ concentration, often initiated by an action potential arriving at the muscle cell membrane. This initial Ca2+ influx triggers a positive feedback loop, amplifying the calcium release from the SR.

2. **Channel Structure:** RyR channels are tetramers, meaning they are composed of four identical protein subunits. Each subunit contains a large cytosolic domain responsible for binding to regulatory proteins, including Ca2+, calmodulin, and FK506-binding proteins (FKBPs). These proteins fine-tune the channel's activity.

3. **Gating:** The opening and closing of RyR channels, also known as gating, is controlled by the conformational changes within the protein structure. These conformational changes are influenced by the binding of various regulatory molecules, including Ca2+, ATP, and other signaling molecules.

4. **Regulation:** RyR channels are tightly regulated by a multitude of factors to ensure precise control of calcium signaling. These include:
- **Ca2+ sensitivity:** The channel's sensitivity to Ca2+ is crucial for the positive feedback loop, but it also makes the channel prone to excessive activation, leading to muscle dysfunction.
- **Phosphorylation:** Phosphorylation of RyR channels by various kinases can modulate their activity, influencing the rate and duration of calcium release.
- **FKBPs:** FKBPs interact with the channel, stabilizing its closed state and preventing uncontrolled calcium release.
- **Other modulators:** A variety of other signaling molecules, including nitric oxide and reactive oxygen species, can also influence RyR channel activity.

5. **Physiological Significance:** Ryanodine-sensitive calcium-release channel activity is essential for muscle contraction, excitation-contraction coupling, and other cellular processes. Disruptions in RyR function can lead to various muscle disorders, including malignant hyperthermia, heart failure, and skeletal muscle weakness.

Overall, Ryanodine-sensitive calcium-release channel activity is a complex and tightly regulated process that plays a crucial role in maintaining proper muscle function and cellular homeostasis. The intricate molecular interactions involved in the activation, gating, and regulation of these channels highlight the importance of precise calcium signaling in biological systems.'
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Proteins (3)

Compounds (7)