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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 31

Module 2: Figure Ca 2 + modules

AGONIST

1 Ca 2+
ROC

Second messengers
2 SMOC
2+
Ca

VOC
2+
Ca
3
V

RYR1
SR
4

V Ca 2+

2+ RYR2
Ca
SR
5

V Ca 2+

InsP R
InsP 3
3
ER
AGONIST
6
Ca 2+

Ca 2 + signalling modules.
Some of the main Ca 2 + signalling modules that cells employ to generate Ca 2 + signals are depicted. Ca 2 + is either derived from the external medium
or released from internal stores such as the sarcoplasmic reticulum (SR) in muscle or the endoplasmic reticulum (ER) in other cell types. The ion
channels responsible for gating Ca 2 + in these different modules are explained in the text.

normal circumstances, however, the fully energized OFF act as a buffer, and this applies to the sensors. However,
reactions can rapidly reduce the pulse of Ca 2 + introduced the concentration of these sensors is usually rather low,
by the ON mechanisms, thus generating a brief Ca 2 + so they have little buffering capacity. The role of Ca 2 +
transient (Module 2: Figure Ca 2 + transient mechanisms). buffering is carried out by the other major group of Ca 2 + -
Such brief pulses of Ca 2 + are a characteristic feature binding proteins. Cells have a number of buffers (Module
of the Ca 2 + signalling pathway and contribute to the 2: Table Ca 2 + signalling toolkit) that are capable of bind-
spatiotemporal aspects of Ca 2 + signalling. ing to Ca 2 + both in the cytoplasm and within the lumen
of the endoplasmic reticulum (ER). The sole function of
Ca 2 + buffers these Ca 2 + buffers is to bind Ca 2 + , and this has an im-
Cells express a large number of Ca 2 + -binding proteins, portant function in shaping both the spatial and temporal
which fall into two main groups: Ca 2 + sensors and Ca 2 + properties of Ca 2 + signals.
buffers. The Ca 2 + sensors respond to changes in intracel- The major cytosolic buffers in cells are parvalbumin
lular Ca 2 + by activating some downstream effector pro- (PV), calbindin D-28k (CB) and calretinin (CR).The
cess. In a sense, all proteins capable of binding Ca 2 + will major buffers that operate within the lumen of the ER

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