Page last updated: 2024-10-24

calcium ion import into cytosol

Definition

Target type: biologicalprocess

The directed movement of calcium ion into a cytosol. [GO_REF:0000075, GOC:TermGenie, GOC:vw]

Calcium ion import into the cytosol is a tightly regulated process that plays a crucial role in a wide range of cellular functions, including muscle contraction, neurotransmitter release, signal transduction, and gene expression. Here's a detailed breakdown of the process:

**1. Calcium Channels:** The first step in calcium ion import is the opening of calcium channels in the plasma membrane or the membranes of intracellular organelles like the endoplasmic reticulum (ER) and mitochondria. These channels act as selective pores that allow the passage of calcium ions into the cytosol while blocking other ions. There are different types of calcium channels with varying mechanisms of activation and localization:

* **Voltage-gated calcium channels (VGCCs):** These channels open in response to changes in membrane potential, often triggered by depolarization events. They are primarily found in excitable cells like neurons and muscle cells.
* **Ligand-gated calcium channels (LGCCs):** These channels open in response to the binding of specific signaling molecules, such as neurotransmitters or hormones. For example, acetylcholine binds to nicotinic acetylcholine receptors, which are LGCCs, leading to calcium influx into muscle cells.
* **Store-operated calcium channels (SOCCs):** These channels open in response to depletion of calcium from intracellular stores, particularly the ER. They are activated by the calcium sensor protein STIM1, which resides in the ER membrane and senses calcium levels.

**2. Calcium Ion Flux:** Once the calcium channels are open, calcium ions flow down their electrochemical gradient, moving from the higher concentration in the extracellular space or intracellular stores to the lower concentration in the cytosol. This movement of calcium ions is driven by both the concentration gradient and the electrical potential across the membrane.

**3. Calcium Pumps and Transporters:** To maintain calcium homeostasis and prevent excessive calcium accumulation in the cytosol, cells utilize various mechanisms to remove calcium from the cytosol. These include:

* **Plasma membrane calcium ATPase (PMCA):** This pump actively transports calcium ions out of the cell, using ATP as an energy source. It plays a crucial role in maintaining low intracellular calcium levels.
* **Sodium-calcium exchanger (NCX):** This transporter exchanges sodium ions for calcium ions across the plasma membrane. The movement of sodium ions down their electrochemical gradient provides the energy for calcium extrusion.
* **Sarco/endoplasmic reticulum calcium ATPase (SERCA):** This pump actively transports calcium ions from the cytosol into the lumen of the ER, using ATP as an energy source. The ER serves as a major calcium storage site, and SERCA plays a vital role in refilling these stores after calcium release.

**4. Calcium Binding Proteins:** Inside the cytosol, calcium ions interact with various proteins, triggering a cascade of downstream signaling events. These proteins often contain specific binding sites for calcium and undergo conformational changes upon calcium binding. Some key calcium-binding proteins include:

* **Calmodulin:** This ubiquitous protein binds to calcium and undergoes a conformational change, activating various downstream targets, including kinases, phosphatases, and transcription factors.
* **Troponin:** This protein is involved in muscle contraction and binds to calcium, leading to the exposure of myosin binding sites on actin filaments.
* **Synaptotagmin:** This protein is crucial for neurotransmitter release and binds to calcium, triggering vesicle fusion and neurotransmitter release at synapses.

**5. Calcium Signaling Pathways:** The influx of calcium ions into the cytosol can initiate diverse signaling pathways that regulate various cellular processes:

* **Muscle Contraction:** In muscle cells, calcium ions bind to troponin, leading to the contraction of muscle fibers.
* **Neurotransmitter Release:** In neurons, calcium ions trigger the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft.
* **Gene Expression:** Calcium signaling can activate specific transcription factors, regulating the expression of genes involved in various cellular processes.
* **Cell Proliferation and Differentiation:** Calcium signaling plays a role in cell growth, differentiation, and apoptosis.

**6. Calcium Homeostasis:** Maintaining tight control over calcium levels is crucial for cell survival and proper functioning. Dysregulation of calcium homeostasis can lead to a range of diseases, including muscle disorders, neurological diseases, and cancer.

The complex interplay of calcium channels, pumps, transporters, binding proteins, and signaling pathways ensures that calcium ions are tightly regulated, enabling cells to respond effectively to internal and external stimuli.'
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Proteins (1)

ProteinDefinitionTaxonomy
Transient receptor potential cation channel subfamily V member 4A transient receptor potential cation channel TRPV4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q9HBA0]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
cannabinolCannabinol: A physiologically inactive constituent of Cannabis sativa L.dibenzopyran
cannabichromene1-benzopyran
(6ar-trans)-isomer of tetrahydrocannabivarin 9
hc 0300312-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide: a TRPA1 channel blocker
hc-067047HC-067047: a TRPA1 antagonist; structure in first source
rn 1734RN 1734: a TRPV4 antagonist; structure in first source
cannabigerolcannabigerol : A member of the class of resorcinols that is resorcinol which is substituted by a (2E)-3,7-dimethylocta-2,6-dien-1-yl group at position 2 and by a pentyl group at position 5. It is a natural product found in Cannabis sativa and Helichrysum species.

cannabigerol: RN given refers to (E)-isomer; structure given in first source
phytocannabinoid;
resorcinols
anti-inflammatory agent;
antibacterial agent;
antioxidant;
appetite enhancer;
cannabinoid receptor agonist;
neuroprotective agent;
plant metabolite
cannabidivarincannabidivarin: from Cannabis sativamonoterpenoid
gsk 1016790aGSK1016790A : A tertiary carboxamide that is piperazine in which one of the amino groups has undergone condensation with the carboxy group of N-[(2,4-dichlorophenyl)sulfonyl]-L-serine, while the other has undergone condensation with the carboxy group of N-(1-benzothiophen-2-ylcarbonyl)-L-leucine. It is a cell-permeable, potent and selective agonist of the TRPV4 (transient receptor potential vanilloid 4) channel.1-benzothiophenes;
aromatic primary alcohol;
dichlorobenzene;
N-acylpiperazine;
sulfonamide;
tertiary carboxamide
TRPV4 agonist