regulation of release of sequestered calcium ion into cytosol

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria. [GOC:ai, GOC:tb]

The regulation of the release of sequestered calcium ions into the cytosol is a complex and finely tuned process essential for a wide range of cellular functions. Calcium ions (Ca2+) are crucial second messengers involved in signaling pathways that control muscle contraction, neurotransmitter release, gene expression, and many other cellular processes. The majority of intracellular Ca2+ is stored within organelles, primarily the endoplasmic reticulum (ER) in most cells and the sarcoplasmic reticulum (SR) in muscle cells. The release of Ca2+ from these intracellular stores is tightly regulated by a specialized machinery that ensures rapid and localized Ca2+ signaling.

Here is a detailed description of the biological process of regulation of release of sequestered calcium ions into the cytosol:

**1. Ca2+ Sequestration:**

- Ca2+ is actively pumped into the ER and SR lumen by Ca2+-ATPases. These proteins use the energy derived from ATP hydrolysis to move Ca2+ against its electrochemical gradient, creating a high concentration of Ca2+ within these organelles.
- The ER/SR lumen contains specialized proteins that bind Ca2+, such as calreticulin and calsequestrin, which serve as a buffer to prevent excessive Ca2+ accumulation.

**2. Ca2+ Release Channels:**

- The release of Ca2+ from the ER/SR is mediated by specific Ca2+ channels. The most important of these channels is the inositol 1,4,5-trisphosphate receptor (IP3R) and the ryanodine receptor (RyR).
- IP3Rs are activated by the intracellular messenger IP3, which is produced in response to various stimuli, such as hormones, neurotransmitters, and growth factors.
- RyRs are activated by Ca2+ itself, in a process known as Ca2+-induced Ca2+ release (CICR). CICR is a positive feedback mechanism that amplifies Ca2+ signals.

**3. Ca2+ Release Mechanisms:**

- **IP3R-mediated Ca2+ release:** IP3 binds to IP3Rs on the ER membrane, causing a conformational change that opens the channel. This allows Ca2+ to flow from the ER lumen into the cytosol.
- **RyR-mediated Ca2+ release:** RyRs are located on the SR membrane in muscle cells and are responsible for the rapid release of Ca2+ that triggers muscle contraction. RyRs are activated by a rise in cytosolic Ca2+, creating a positive feedback loop.
- **Other Ca2+ release mechanisms:** Other Ca2+ channels, such as the transient receptor potential (TRP) channels, can also contribute to Ca2+ release from intracellular stores in specific cell types.

**4. Ca2+ Signaling:**

- Once released into the cytosol, Ca2+ binds to various target proteins, triggering a cascade of downstream signaling events. These events include:
- **Muscle contraction:** Ca2+ binds to troponin, a protein that regulates the interaction between actin and myosin filaments, leading to muscle contraction.
- **Neurotransmitter release:** Ca2+ influx into the presynaptic terminal triggers the fusion of synaptic vesicles with the plasma membrane, releasing neurotransmitters into the synaptic cleft.
- **Gene expression:** Ca2+ activates transcription factors, such as calcineurin and NFAT, which regulate gene expression.
- **Cell proliferation and differentiation:** Ca2+ plays a role in various cell growth and differentiation processes.

**5. Ca2+ Replenishment and Homeostasis:**

- After Ca2+ release, the ER/SR must replenish its Ca2+ stores to maintain Ca2+ homeostasis.
- This is accomplished by the continuous action of Ca2+-ATPases, which pump Ca2+ back into the ER/SR lumen.
- In addition, Ca2+ can be taken up from the extracellular space by various plasma membrane Ca2+ channels.

**6. Regulation of Ca2+ Signaling:**

- The release and re-uptake of Ca2+ are tightly regulated to ensure precise and localized Ca2+ signaling.
- Various mechanisms contribute to this regulation:
- **IP3 production and degradation:** The production of IP3 is regulated by upstream signaling pathways, and IP3 is rapidly degraded by enzymes, limiting Ca2+ release.
- **Ca2+ feedback mechanisms:** Ca2+ itself can regulate its own release through CICR and by inhibiting IP3R activity.
- **Ca2+ binding proteins:** Proteins such as calmodulin bind Ca2+ and regulate the activity of downstream signaling pathways.

**7. Dysregulation of Ca2+ Homeostasis:**

- Dysregulation of Ca2+ homeostasis can have detrimental effects on cellular function.
- Abnormally high cytosolic Ca2+ levels can lead to apoptosis, necrosis, and other cellular dysfunctions.
- Deficiencies in Ca2+ signaling can impair muscle contraction, neurotransmitter release, and other processes.

The regulation of Ca2+ release from intracellular stores is a crucial process that ensures the proper functioning of cells. Disruptions in this process can lead to a wide range of diseases. Understanding the molecular mechanisms underlying Ca2+ signaling is essential for developing new therapeutic strategies for these diseases.
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Compounds (948)