negative regulation of calcium-mediated signaling

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of calcium-mediated signaling. [GOC:ai, PMID:11696592]

Negative regulation of calcium-mediated signaling is a complex process that involves a variety of mechanisms to control the intracellular concentration of calcium ions (Ca2+), a key second messenger involved in diverse cellular processes. This regulation is crucial for maintaining cellular homeostasis and ensuring appropriate responses to stimuli.

The primary goal of this regulation is to prevent excessive calcium influx and signaling, which can lead to cellular dysfunction or even cell death. Here's a breakdown of the main mechanisms involved:

1. **Calcium Channel Modulation:**
- **Voltage-gated calcium channels (VGCCs):** These channels open in response to membrane depolarization, allowing Ca2+ influx. Their activity can be modulated by various factors, including phosphorylation, membrane potential, and interaction with regulatory proteins.
- **Ligand-gated calcium channels:** These channels are activated by the binding of specific ligands, such as neurotransmitters or hormones. Their regulation involves ligand binding affinity, receptor desensitization, and downstream signaling pathways.
- **Store-operated calcium channels (SOCs):** These channels are activated by depletion of Ca2+ from intracellular stores. They play a crucial role in replenishing Ca2+ levels and are regulated by a complex interplay between proteins like STIM1 and Orai1.

2. **Calcium Pumps and Transporters:**
- **Plasma membrane Ca2+ ATPase (PMCA):** This pump actively removes Ca2+ from the cytosol to the extracellular space, maintaining low cytosolic Ca2+ levels. Its activity is regulated by phosphorylation, Ca2+ concentration, and interaction with regulatory proteins.
- **Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA):** This pump actively transports Ca2+ from the cytosol into the endoplasmic reticulum (ER), the main intracellular calcium store. SERCA activity is regulated by Ca2+ concentration, phosphorylation, and interaction with regulatory proteins.
- **Sodium-calcium exchanger (NCX):** This transporter uses the electrochemical gradient of sodium ions (Na+) to move Ca2+ out of the cell. Its activity is regulated by membrane potential, Ca2+ concentration, and Na+ concentration.

3. **Calcium Buffering:**
- **Calcium-binding proteins:** These proteins bind Ca2+ in the cytosol, reducing free Ca2+ concentration and buffering its fluctuations. They include calmodulin, parvalbumin, and calbindin.

4. **Signal Transduction Pathways:**
- **Calcium-dependent signaling pathways:** These pathways involve the activation of Ca2+-dependent enzymes, such as protein kinases and phosphatases, which modify the activity of downstream targets.
- **Negative feedback loops:** These loops are essential for fine-tuning Ca2+ signaling and preventing overactivation. They involve Ca2+-dependent mechanisms that inhibit Ca2+ influx or promote Ca2+ extrusion.

5. **Cellular Processes:**
- **Muscle contraction:** Ca2+ plays a crucial role in muscle contraction by binding to troponin, triggering the sliding filament mechanism. Regulation of Ca2+ levels is essential for smooth and controlled muscle activity.
- **Neurotransmission:** Ca2+ influx at synapses triggers neurotransmitter release, enabling communication between neurons. Negative regulation of Ca2+ signaling is crucial for preventing excessive neurotransmitter release and maintaining synaptic plasticity.
- **Gene expression:** Ca2+ can activate gene expression by modulating transcription factor activity.

In summary, negative regulation of calcium-mediated signaling is a dynamic process involving multiple mechanisms that tightly control intracellular Ca2+ levels. This regulation is essential for maintaining cellular homeostasis, ensuring proper responses to stimuli, and preventing cellular dysfunction.'
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Proteins (3)

Compounds (5)