Calcium

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Calcium is used in many different signaling pathways, i.e. G proteinsion channels etc.

The basic concentrations of calcium ions are : 100 nM inside the cell and 2 to 3 mM outside the cell. Although there is a huge gradient forcing calcium to move from outside to inside, it does not move that way. 

Every person starts out as a calcium wave. The wave triggered during fertilisation stops multiple sperm from fertilizing the ovum,  this is known as the fertilisation envelope. Ca2+ signalling within a cell can be very complicated and it can be hard to understand what is going on as it is involved in numerous pathways. This brings about the complication of cross talk between messengers [1] . The fertlisation process and the role that calcium plays is one of the few that is understood. The calcium signal will only be released once a mature oocyte is created and not earlier, this starts off the developmental cycle. When an ovum becomes fertlized, the machinery required for calcium signalling undergoes a conformational change, which enables the signal to be released [2].

Calcium is used as an intracellular messenger as it is kept at low levels in resting cells; cells have many sensitive mechanisms that detect rises and falls in calcium levels. These include a number of "OFF" and "ON" mechanisms.

"OFF" mechanisms are important in the recovery of intracellular calcium levels, particularly in muscle cells, as the cell cannot contract again until calcium levels fall after the rise associated with contraction. "OFF" mechanisms include buffer proteins in the sarcoplasmic reticulum (SR) (e.g. calsequestrin). These proteins have low affinity and high capacity for calcium, so that it is still easily released for signalling. Another "OFF" mechanism is Na+/Ca2+ exchanger pump in the plasma membrane, which operates at higher levels of Ca2+. The differences in affinity of the "OFF" mechanisms for calcium allow the cell to respond effectively to different concentrations. PMCA and SERCA also keep cytosolic Ca2+ levels low by utilising ATP to pump Ca2+ out of the cytosol into the Endoplasmic reticulum (ER), SR, or outside the cell.

"ON" mechanisms respond to extracellular signals indicating to increase the levels of cytosolic Ca2+. These include InsP3 and Ryanodine receptors, both which are activated by the binding of ATP, however, InsP3 receptors also require binding of the coagonist InsP3 to activate them [3]. The binding of ATP is not itself a driving process but this is just a way to check that the cell has enough energy.

The major pathway in calcium signalling is the Phosphoinositide pathway (PI). This uses the second messenger IP3  to bind to the IP3 receptor and release calcium from the endoplasmic reticulum. The calcium release can cause more calcium release known as calcium induced calcium release (CICR) wich creates the calcium wave.

When there is excessive calcium in a cell , that is when all the OFF mechanisms are saturated, the cell undergoes apoptosis

References:

  1. Machaca, K.,2011. Ca(2+) signaling, genes and the cell cycle. Cell Calcium, 49(5):323-30
  2. Whitaker, M. 2006. Calcium at fertilization and in early development. Physiological reviews, 86(1):25-88
  3. Heldin C. and Purton M,(1996) "Signal Transduction", Chapman and Hall, London
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