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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 32

Module 2: Figure Ca 2 + -induced Ca 2 + release

Stimulus

VOC ROC

Ca 2+ InsP 3
Intracellular CICR
calcium wave
+ + + + +
CICR CICR
+ + +
Spark Puff +
R R R I I I
Blink
+ + + + + +
Ca 2+ ER

The role of Ca 2 + -induced Ca 2 + release (CICR) in mobilizing Ca 2 + from internal stores.
The Ca 2 + -sensitive channels are the ryanodine receptors (R) and the InsP 3 receptors (I) located on the endoplasmic reticulum (ER). CICR has two
important functions. Firstly, it provides a mechanism for transferring information from the plasma membrane to these internal release channels. The
primary mechanism is based on the voltage-operated channels (VOCs) that open in response to membrane depolarization to allow a small amount
of Ca 2 + to enter, which then diffuses into the cell to activate either R or I. The other important function of CICR is to link together these intracellular
channels so that the Ca 2 + being released from one channel diffuses across to neighbouring channels that are excited to release further Ca 2 + , thereby
setting up regenerative waves (yellow arrows).

Module 2: Figure Ca 2 + transient mechanisms

2+
Ca entry
2+
Ca release
2+
Ca buffers
Mitochondria
+
2+
Na /Ca exchanger
2+
Ca pumps
(SERCA/PMCA)
ON OFF
Reactions Reactions

CALCIUM TRANSIENT

The sequence of ON and OFF reactions during the generation of a typical Ca 2 + transient.
The rising phase of the Ca 2 + spike results from the activation of Ca 2 + entry and release mechanisms (yellow bars), which are then terminated by
inactivation processes. Once the ON reactions have been inactivated, a series of OFF reactions operate in a sequential manner to restore Ca 2 + to
its resting level (blue bars). During the rising phase of the Ca 2 + transient, large amounts of Ca 2 + are rapidly bound to the Ca 2 + buffers (calbindin
D-28k and parvalbumin) and are taken up by the mitochondria. The mitochondria and cytosolic buffers help to shape the Ca 2 + signal by reducing
the impact of the ON reactions. In effect, they enable the cell to generate very fast transients without running the risk of being overwhelmed by Ca 2 + .

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