negative regulation of calcium ion import across plasma membrane

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of calcium ion import across plasma membrane. [GO_REF:0000058, GOC:bhm, GOC:TermGenie, PMID:17640527]

Negative regulation of calcium ion import across the plasma membrane is a critical cellular process that controls the influx of calcium ions (Ca2+) into the cell. Ca2+ is a ubiquitous intracellular signaling molecule that plays essential roles in a wide range of cellular functions, including muscle contraction, neurotransmitter release, enzyme activation, and gene expression. However, excessive intracellular Ca2+ levels can be detrimental, leading to cell death and various pathologies. Therefore, tight regulation of Ca2+ import is crucial for maintaining cellular homeostasis.

The plasma membrane, which acts as a barrier between the cell's interior and its external environment, is equipped with various proteins that mediate Ca2+ influx. These proteins include voltage-gated calcium channels, ligand-gated calcium channels, and store-operated calcium channels. The activity of these channels is regulated by a complex interplay of intracellular and extracellular signaling pathways, ensuring that Ca2+ import occurs only when needed and at appropriate levels.

Negative regulation of Ca2+ import across the plasma membrane involves mechanisms that suppress or inhibit the activity of Ca2+ channels. These mechanisms include:

1. **Inactivation of Ca2+ channels:** Once activated, certain Ca2+ channels undergo a process known as inactivation, which reduces their permeability to Ca2+. This is a short-term mechanism that helps to prevent excessive Ca2+ influx.

2. **Phosphorylation of Ca2+ channels:** Phosphorylation of Ca2+ channels by specific kinases can either activate or inhibit their activity, depending on the channel type and the kinase involved. In some cases, phosphorylation leads to decreased Ca2+ permeability, contributing to negative regulation.

3. **Binding of inhibitory proteins:** Some proteins bind to Ca2+ channels, inhibiting their function. These inhibitory proteins can act by physically blocking the channel pore, altering the channel's conformation, or interfering with the channel's interaction with other signaling molecules.

4. **Depletion of intracellular Ca2+ stores:** Calcium stores within the endoplasmic reticulum (ER) can be depleted, triggering a decrease in store-operated calcium channel (SOCC) activity. SOCCs are responsible for Ca2+ influx in response to depletion of ER Ca2+ stores, so their inhibition indirectly contributes to negative regulation of Ca2+ import.

5. **Activation of Ca2+-activated potassium channels:** The activation of certain potassium channels by increased intracellular Ca2+ levels can lead to hyperpolarization of the plasma membrane, reducing the driving force for Ca2+ influx through voltage-gated calcium channels.

6. **Modulation of Ca2+ pumps:** Plasma membrane Ca2+ pumps actively transport Ca2+ out of the cell, counteracting Ca2+ influx. The activity of these pumps can be modulated by various signaling pathways, contributing to the regulation of overall Ca2+ levels.

These mechanisms, acting in concert, ensure that Ca2+ import across the plasma membrane is tightly regulated, maintaining cellular homeostasis and preventing pathological consequences of Ca2+ overload.'
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Proteins (3)

Compounds (4)