Calcium signaling

Calcium signaling is the use of

Concentration regulation

The resting concentration of Ca²⁺ in the

Specific signals can trigger a sudden increase in the cytoplasmic Ca²⁺ levels to 500–1,000 nM by opening channels in the ER or the

1. Many
   G protein-coupled receptors and receptor tyrosine kinases
   , activate the PLC enzyme.
2. PLC uses
   diacylglycerol
   (DAG), two classic secondary messengers.
3. DAG attaches to the plasma membrane and recruits protein kinase C (PKC).
4. IP₃ diffuses to the ER and is bound to the
   IP3 receptor
   .
5. The IP₃ receptor serves as a Ca²⁺ channel, and releases Ca²⁺ from the ER.
6. The Ca²⁺ bind to PKC and other proteins and activate them.^[4]

Depletion from the endoplasmic reticulum

Depletion of Ca²⁺ from the ER will lead to Ca²⁺ entry from outside the cell by activation of "Store-Operated Channels" (SOCs).^[5] This inflow of Ca²⁺ is referred to as Ca²⁺-release-activated Ca²⁺ current (ICRAC). The mechanisms through which ICRAC occurs are currently still under investigation. Although Orai1 and STIM1, have been linked by several studies, for a proposed model of store-operated calcium influx. Recent studies have cited the phospholipase A2 beta,^[6] nicotinic acid adenine dinucleotide phosphate (NAADP),^[7] and the protein STIM 1^[8] as possible mediators of ICRAC.

As a second messenger

Calcium is a ubiquitous

Many of Ca²⁺ mediated events occur when the released Ca²⁺ binds to and activates the regulatory protein calmodulin. Calmodulin may activate the Ca²⁺-calmodulin-dependent protein kinases, or may act directly on other effector proteins.^[14] Besides calmodulin, there are many other Ca²⁺-binding proteins that mediate the biological effects of Ca²⁺.

In muscle contractions

Contractions of skeletal muscle fiber are caused due to electrical stimulation. This process is caused by the depolarization of the transverse tubular junctions. Once depolarized the sarcoplasmic reticulum (SR) releases Ca²⁺ into the myoplasm where it will bind to a number of calcium sensitive buffers. The Ca²⁺ in the myoplasm will diffuse to Ca²⁺ regulator sites on the thin filaments. This leads to the actual contraction of the muscle.^[15]

Contractions of smooth muscle fiber are dependent on how a Ca²⁺ influx occurs. When a Ca²⁺ influx occurs,

The ER, in neurons, may serve in a network integrating numerous extracellular and intracellular signals in a binary membrane system with the plasma membrane. Such an association with the plasma membrane creates the relatively new perception of the ER and theme of "a neuron within a neuron." The ER's structural characteristics, ability to act as a Ca²⁺ sink, and specific Ca²⁺ releasing proteins, serve to create a system that may produce regenerative waves of Ca²⁺ release. These may communicate both locally and globally in the cell. These Ca²⁺ signals integrate extracellular and intracellular fluxes, and have been implicated to play roles in synaptic plasticity, memory, neurotransmitter release, neuronal excitability, and long term changes at the gene transcription level. ER stress is also related to Ca²⁺ signaling and along with the unfolded protein response, can cause ER associated degradation (ERAD) and autophagy.^[19]

Astrocytes have a direct relationship with neurons through them releasing gliotransmitters. These transmitters allow communication between neurons and are triggered by calcium levels increasing around astrocytes from inside stores. This increase in calcium can also be caused by other neurotransmitters. Some examples of gliotransmitters are ATP and glutamate. ^[20] Activation of these neurons will lead to an increase in the concentration of calcium in the cytosol from 100 nanomolar to 1 micromolar.^[21]

In fertilization

Ca²⁺ influx during fertilization has been observed in many species as a trigger for development of the oocyte. These influxes may occur as a single increase in concentration as seen with fish and echinoderms, or may occur with the concentrations oscillating as observed in mammals. The triggers to these Ca²⁺ influxes may differ. The influx have been observed to occur via membrane Ca²⁺ conduits and Ca²⁺ stores in the sperm. It has also been seen that sperm binds to membrane receptors that lead to a release in Ca²⁺ from the ER. The sperm has also been observed to release a soluble factor that is specific to that species. This prevents cross species fertilization to occur. These soluble factors lead to activation of IP₃ which causes a Ca²⁺ release from the ER via IP₃ receptors.^[22] It has also been seen that some model systems mix these methods such as seen with mammals.^[23][24] Once the Ca²⁺ is released from the ER the egg starts the process of forming a fused pronucleus and the restart of the mitotic cell cycle.^[25] Ca²⁺ release is also responsible for the activation of NAD⁺ kinase which leads to membrane biosynthesis, and the exocytosis of the oocytes cortical granules which leads to the formation of the hyaline layer allowing for the slow block to polyspermy.

See also

• Nanodomain
• European Calcium Society

References

Further reading

• Petersen OH (2005). "Ca2+ signalling and Ca2+-activated ion channels in exocrine acinar cells". Cell Calcium. 38 (3–4): 171–200.
  PMID 16107275
  .

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