How does calcium trigger the release of neurotransmitters
Calcium s [from Latin. calx, Gen. calcis = lime], Calcium,E. calcium, chemical symbol Ca, universally occurring alkaline earth metal, its meaning mainly in the ionic form as Approx2+(Calcium ion) (see additional information). Calcium fulfills important tasks in the nervous system. The release of neurotransmitters from presynaptic storage vesicles is strictly dependent on the pattern of the calcium influx triggered by action potentials. On the postsynaptic membrane, in turn, Ca is used to open ion channels when exposed to acetylcholine. As a secondary messenger, Ca also converts the information received from peptide hormones and neurotransmitters into intracellular biochemical processes. These are e.g. the activation of enzyme cascades (adenylate cyclase, Ras) and calcium-binding proteins, the most important of which are the Calmodulin that occurs as a subunit in enzymes (especially protein kinases) (see additional information). There are two classes of such calcium-dependent protein kinases in the brain, the calcium calmodulin kinases (CaMK) and the calcium / diacylglycerol-dependent kinase (protein kinase C). Calcium / calmodulin-induced processes also include the activation of transcription factors such as CREB, whereby the duration and frequency of calcium influx via NMDA receptors (glutamate receptors) or via voltage-regulated calcium channels (L-type) leads to differential gene expression. The calcium calmodulin kinase cascade plays an important role in synaptic plasticity and memory formation. In the growth cones of nerve cells, a sufficiently high calcium level is necessary for neurites to sprout. On the other hand, an overload of neurons with calcium, e.g. after a stroke, in epilepsy or after axon injury (via NMDA receptors or from mitochondria), is an important cause of neuronal cell death (excitotoxicity). Calcium-dependent proteases (calpain) or endonucleases, which break down cellular molecules, or radical-forming enzymes such as nitric oxide synthase and phospholipase A2 are activated. The use of calcium blockers in neurodegenerative diseases has so far been unsuccessful. Hippocampal interneurons with calcium-binding proteins such as calbindin or parvalbumin can sequester free cytoplasmic calcium well and are particularly resistant to ischemic damage (ischemia).
Role of calcium in signal transduction:
Approx2+-Ions are found in the cytoplasm (mammalian cell) in very low concentrations (≤ 0.1 μmol / l), but in much higher concentrations (1 mmol / l) in the extracellular space. The Ca.2+- levels in the cytoplasm rise sharply; in electrically excitable cells by approx2+-Channels in the plasma membrane from the outside, in other cells by Ca2+-Release from the endoplasmic reticulum (ER). By corresponding approx2+Pumps (approx2+-ATPases) in the plasma membrane or in the ER, the low concentration in the cytoplasm is restored. Approx2+-Ions usually do not act directly, but in connection with the Ca2+-binding protein Calmodulin on cellular events. By binding approx2+-Ions, calmodulin is changed in its conformation so that it can bind to various proteins (protein kinases and protein phosphatases) and thus regulate their activity. Inositol triphosphate (IP3) causes the release of Ca2+-Ions from the ER; that together with IP3 The released diacylglycerol activates the calcium-dependent protein kinase C. - Ca ions play a central role as mediators between excitation and contraction in the actomyosin system of muscles. The active forms of movement of phagocytosis, pinocytosis and exocytosis perceived by individual cells are also calcium-dependent processes. The temporal coordination of such Ca effects, in which contraction and relaxation alternate with one another, is often described using the model of the biological oscillator. Here, the intracellular concentrations of Ca and cAMP are coupled via two opposing control loops. cAMP inhibits the calcium pump, which lowers the intracellular calcium level, while Ca activates adenylate cyclase, which catalyzes the formation of cAMP.
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