Calcium concentration microdomains (CCMs) are sites in a cell's
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
with a localised high
calcium ion (Ca
2+) concentration.
They are found immediately around the intracellular opening of
calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...
s; when a calcium channel opens, the Ca
2+ concentration in the adjacent CCM increases up to several hundred
micromolar (μM).
These microdomains take part in
calcium signaling, which has a diverse range of potential outcomes.
Calcium concentration microdomains can be visualised with
fluorescence microscopy by using
aequorin as a reporter protein.
Ion Channel Process
The actions of the
Na-K-ATPase enzyme relate with the creation of calcium-signaling microdomains.
Na-K-ATPase is a protein that pumps
Na+ and
K+ across the cell membrane. Na-K-ATPase helps to keep the body at equilibrium by the movement of those ions through the plasma membrane. This ion pump helps to reset the movement of ions during an
action potential
An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...
by sending K
+ into the cell and sending Na
+ out of the cell. Since it opposes the normal flow of ions during an action potential, energy in the form of ATP (
adenosine triphosphate
Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...
) is used. Calcium is also regulated using this Na-K-ATPase due to the enzyme's interactions with protein and non-protein molecules.
The main interaction that keeps calcium regulated is the binding of Na-K-ATPase to inositol 1,4,5-trisphosphate (
IP3). IP3 is a
secondary messenger that helps to send neuronal signals through the body. The neuronal cells have the calcium-signaling microdomains in the
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
right next to the pre- and post-synaptic calcium channels in the nerve cells. Figure 1 is an example of how Na-K-ATPase forms the calcium-signaling microdomain.
The
astrocytes
Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...
which are star-shaped glial cells in the central nervous system are the main cells with these calcium-signaling micro domains. In fact, a rigorous mathematical analysis in
astrocytes
Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...
has shown that localized inflow of Ca
2+ remains localized, despite the diffusion of cytosolic Ca
2+ and potential storage in the endoplasmic reticulum.
A Na
+/Ca
2+ exchanger (
NCX) is also involved in regulating the amount of calcium in cells. The NCX switches the intra- and extra-cellular amounts of Na
+ and Ca
2+. NCX works together with Na-K-ATPase to create calcium concentration microdomains in certain cells like astrocytes discussed above. Specific forms of Na-K-ATPase, the α2 or α3 isoforms, actually interact with the NCX in the formation of the calcium microdomains in astrocytes.
Neurological Interactions
Astrocytes
Muscular Interactions
Muscle Cells
Footnotes
References
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Cellular neuroscience