intracellular calcium ion homeostasis

Definition

Target type: biologicalprocess

A homeostatic process involved in the maintenance of a steady state level of calcium ions within a cell. [GOC:ceb, GOC:mah]

Intracellular calcium ion homeostasis is a tightly regulated process that maintains the appropriate concentration of calcium ions (Ca2+) within the cytoplasm of cells. Ca2+ is a ubiquitous second messenger that plays a crucial role in a wide range of cellular functions, including muscle contraction, neurotransmitter release, fertilization, cell proliferation, and apoptosis. To maintain proper cellular function, Ca2+ levels within the cytoplasm must be kept at low concentrations, typically in the nanomolar range, while extracellular Ca2+ concentrations are much higher, in the millimolar range. This steep concentration gradient is maintained by a complex interplay of proteins and mechanisms that control Ca2+ influx, efflux, and storage.

The key components of intracellular Ca2+ homeostasis include:

1. **Plasma Membrane Ca2+ Channels:** These channels regulate the influx of Ca2+ from the extracellular environment. Different types of channels exist, including voltage-gated Ca2+ channels, ligand-gated Ca2+ channels, and store-operated Ca2+ channels. These channels are activated by various stimuli, such as changes in membrane potential, ligand binding, or depletion of intracellular Ca2+ stores.

2. **Plasma Membrane Ca2+ Pumps:** These pumps actively transport Ca2+ out of the cell, maintaining the steep Ca2+ gradient across the plasma membrane. The most prominent Ca2+ pump is the plasma membrane Ca2+-ATPase (PMCA), which uses ATP hydrolysis to pump Ca2+ out of the cell against its concentration gradient.

3. **Endoplasmic Reticulum (ER) Ca2+ Stores:** The ER is the main intracellular Ca2+ storage organelle. Ca2+ is actively transported into the ER lumen by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. The ER contains a high concentration of Ca2+, which can be released into the cytoplasm upon stimulation.

4. **ER Ca2+ Channels:** These channels release Ca2+ from the ER lumen into the cytoplasm. The major ER Ca2+ channel is the inositol 1,4,5-trisphosphate receptor (IP3R), which is activated by the second messenger IP3, produced in response to various stimuli. Another important ER Ca2+ channel is the ryanodine receptor (RyR), which is activated by Ca2+ itself, leading to Ca2+-induced Ca2+ release.

5. **Ca2+ Binding Proteins:** These proteins buffer Ca2+ in the cytoplasm, preventing its accumulation and ensuring that Ca2+ signals are transient and localized. Important Ca2+ binding proteins include calmodulin, troponin C, and parvalbumin.

**Regulation of Intracellular Ca2+ Homeostasis:**

The precise regulation of intracellular Ca2+ levels is essential for proper cell function. Several mechanisms contribute to this regulation:

* **Stimulus-Specific Ca2+ Signaling:** Different stimuli activate specific Ca2+ channels and signaling pathways, leading to distinct Ca2+ responses within the cell. This allows for highly specialized Ca2+ signaling in response to various physiological cues.
* **Ca2+ Feedback Mechanisms:** Ca2+ itself can regulate its own signaling by activating Ca2+ pumps and channels, as well as by binding to Ca2+ binding proteins. These feedback mechanisms help to terminate and fine-tune Ca2+ signals.
* **Spatial Control of Ca2+ Signaling:** Ca2+ signals are often localized to specific regions within the cell, allowing for compartmentalized and targeted responses. This is achieved through the localized expression of Ca2+ channels, pumps, and binding proteins.

**Disruption of Ca2+ Homeostasis:**

Disruptions in intracellular Ca2+ homeostasis can lead to various pathological conditions, including:

* **Muscle disorders:** Altered Ca2+ signaling can cause muscle weakness, fatigue, and cramps.
* **Neurological disorders:** Dysregulation of Ca2+ homeostasis can lead to neurodegeneration, seizures, and cognitive impairment.
* **Cardiovascular diseases:** Abnormal Ca2+ handling in the heart can contribute to arrhythmias and heart failure.

In summary, intracellular Ca2+ homeostasis is a highly complex and tightly regulated process that plays a crucial role in maintaining cellular function. The interplay of Ca2+ channels, pumps, and binding proteins, as well as feedback mechanisms, ensures that Ca2+ signals are precisely controlled in time and space, allowing for diverse and highly specific cellular responses.'
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Proteins (39)

Compounds (1,212)