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Calcium signalling
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Lecture notes of 13 pages for the course Physiology at CF (Calcium signaling)
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Calcium is a unique universal carrier of biological information. It plays key roles in development ofcells and even cell death. Ca2+ has the highest difference in concentration between extra and
intracellular spaces which is almost 10000 times. The importance of Ca2+ is that it precipitates
with phosphate and phosphate is chosen by the cell as a building block for DNA which is again a
building block for the energy source in form of ATP molecules. Calcium is toxic for the cell and cell
always try to get rid of it. So, that’s why it’s an important signalling pathway in cells. Cell has a
storage of calcium which is not containing the calcium in cytoplasm. Calcium has to be permitted
to enter the cell which happens via the channels and pumps. The cytoplasmic calcium can only
rise up to 1 micro M.
The calcium signalling begins when stimulus hormone or neurotransmitter riches the receptor.
After activating the channel’s receptor, it produces the second messenger. Second messenger is
either produced within the cell or activated within the cell or imported into the cell. Second
messenger is usually a small molecule or ion in order to move freely and fast within the cytoplasm
to reach the target site. The channel on the ER/SR is sensitive to calcium and second messenger.
By binding either of them, the channel opens and calcium releases from the lumen to the plasma
resulting into activation of the effectors to start mechanisms within the cell. T has to be noted that
every reaction begins with different concentrations of the calcium in the plasma. After all the
activation process, the cell has to get rid of the calcium due to its toxicity. There are different
methods to remove the Ca from the cell:
Method 1 – remove Ca2+ out of the cell
Plasma membrane Ca2+/ATPase pumps (PMCA) does the key activity in the removal by removing
30 Ca ions per sec which is high affinity for Calcium. It exchanges 1 ion of calcium with 2 protons
by using 1 ATP.
In addition, exchanger molecules are the other way to get rid of the excess Ca. there are 2 types
of exchangers which are Na/Ca K (NCKX) and Na/Ca (NCX) exchangers. Exchangers are
important because of their high rate which is about 2000 ca2+ per sec.
, Method 2- sequestering calcium into intracellular stores
Calcium can be stored in the endoplasmic reticulum/sarcoplasmic reticulum and other organelles
such as the nuclear envelope, endosomes, lysosomes and mitochondria. Mitochondria works as
calcium storage of the cell. Calcium enters the mitochondrial matrix which is also useful for the
mitochondria itself as enzymes producing ATP in the mitochondria cost calcium to do their job.
The responsible exchanger for entering calcium into mitochondria is NCX.
The main storage of calcium in the cell is endoplasmic reticulum (ER).
The ER contains two families of intracellular ca2+ release channels:
Inositol 1,4,5-trisphosphate receptors (IP3Rs)
Ryanodine receptors (RyRs)
Each channel gets activated by special ligands such as Inositol trisphosphate (IP3) which only
affects IP3R channels but the RyR channels get activated by cyclic ADP-ribose (cADPR) and
nicotinic acid adenine dinucleotide phosphate (NAADP).
Method 3- chelating calcium: calcium binding proteins
Calcium buffers are meant to act as a buffer for calcium ions, but they are proteins which are
calbindin (in the brain), and calsequestrin (in the ER/SR).
Sensors:
C2rpotein domains allowing the proteins to bind calcium directly (phospholipase C, PI3K,
Kinase C)
Calcium-binding proteins to interact with calcium (eg calmodulin EF hands)
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