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Calcium Signalling
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Calcium is a very important signalling molecule in the body – it is known as the universal carrier of signals
It is NOT the synthesis of calcium which allows for cell signalling but the changes in cytosolic concentrations
which do so
Calcium is very poisonous to cells to any exposure much be short lived- prolonged exposure to high concentrations
of calcium will cause cell death
The control of the movement of calcium ions can be controlled through Inositol phosphate compounds
Calcium controls a large variety of different pathways in the body – their action is often controlled by calmodulin
Many effectors are controlled through fluctuation of calcium concentrations in the cells

Calcium as a first messenger
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We can see the role of calcium ion in signalling as first messenger when Calcium directly binds to calcium sensing receptor (CaR)
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This receptor was originally discovered in the parathyroid gland and is involved in the regulation of blood calcium levels in order to maintain
homeostasis
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Calcium as a Second Messenger
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Calcium may be considered a second messenger when it enters the cell as a result of the opening of voltage gated channels or channels
which are opened due to variable stimuli
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Voltage-gated ion channels
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Store operated calcium entry channels
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Receptor operated channels
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These are activated through the interaction with ligands
The most prominent ligand which there is in the body is L-glutamate
Glutamate will activate 2 types of receptors
o Ionotropic receptors – ligand-gated, non-specific cation channels
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Can produce a rapid transient depolarisation which induces release of
Calcium from stores
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The ER/SR is a major intracellular store of calcium
• Allows for calcium to be sequestered from the rest of the cell
• Allows for rapid release of that calcium

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The ER has specialised calcium store areas called calciosomes
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This opens the channel and allows Calcium ions to move down their concentration gradient (from within the
Sarcoplasmic reticulum, to the cytoplasm)
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Those are closely related, as such when the voltage
sensitive receptor is activated, it directly interacts and activates RyR
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Six CaM-kinase II proteins are
assembled into a giant ring in which the hub domains interact tightly to produce a central
structure that is surrounded by kinase domains
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calmodulin binds to the regulatory segment and prevents it from inhibiting the kinase
CaM kinase II is autophosphorylated
Phosphatase can deactivate CaM kinase II

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If present, Ca2+/calmodulin will bind the regulatory segment and prevent it from inhibiting the kinase, thereby
locking the kinase in an active state (upper right)
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This autophosphorylation
further activates the enzyme
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Second, it converts the enzyme to a Ca2+-independent form, so that the kinase remains active even after
the Ca2+/calmodulin dissociates from it (lower left)
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The first (upper left) is a compact state, in which the kinase domains interact with the hub, so that the regulatory
segment is buried in the kinase active site and thereby blocks catalytic activity
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Calcium induces Calcium Release

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InsP3Rs are shown arranged in clusters that form discrete release sites within the continuous endoplasmic
reticulum
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Others (in yellow) have not
bound InsP3 and therefore not activated
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B: at higher levels of [InsP3], coordinated openings of several channels (InsP3 liganded) within a cluster is triggered
by Ca2+ release from one channel acting as an activating ligand to stimulate gating of nearby channels through a
process of Ca2+-induced Ca2+ release (CICR)
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Ca2+ released at one cluster can trigger Ca2+
release at adjacent clusters by CICR, leading to the generation of Ca 2+ waves that propagate by successive cycles of
Ca2+ release, diffusion, and CICR

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