Page 49 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

2+
Role of Ca 2+ in Cell Regulation [Ca ] i oscillation is characterized by multi-
2+
ple brief and regular [Ca ] i increases (Ca 2+
2+
The cytosolic Ca 2+ concentration, [Ca ] i, (ca. spikes) in response to certain stimuli or hor-
0.1 to 0.01 µmol/L) is several decimal powers mones (! B). The frequency, not amplitude, of
2+
lower than the extracellular Ca 2+ concentra- [Ca ] i oscillation is the quantitative signal for
2+
tion [Ca ] o (ca. 1.3 mmol/L). This is because cell response. When low-frequency [Ca ] i
2+
Ca 2+ is continuously pumped from the cytosol oscillation occurs, CaM-kinase II, for example,
2+
stores such as the
into intracellular Ca sarcoplasmic reticulum is activated and phosphorylates only its target
and
proteins, but is quickly and completely deacti-
endoplasmic
Fundamentals and Cell Physiology processes occur by primary active transport phosphorylation and progressively delays the
vated (! B1, B3). High-frequency [Ca ] i oscil-
(! p. 17 A), vesicles, mitochondria and nuclei
2+
lation results in an increasing degree of auto-
(?) or is transported out of the cell. Both
2+
(Ca -ATPases) and, in the case of efflux, by ad-
deactivation of the enzyme (! B3). As a result,
ditional secondary active transport through
the activity of the enzyme decays more and
Ca /3 Na antiporters (! A1).
+
2+
more slowly between [Ca ] i signals, and each
2+
To increase the cytosolic Ca concentration,
2+
additional [Ca ] i signal leads to a summation
2+
2+
channels conduct Ca
Ca
2+
of enzyme activity (! B2). As with action
from intracellular
potentials (! p. 46), this frequency-borne,
stores and the extracellular space into the cy-
tosol (! A2). The frequency of Ca
digital all-or-none type of signal transmission
2+
channel
2+
[Ca ] i amplitude, which is influenced by a
! Depolarization of the cell membrane (nerve
number of factors.
and muscle cells);
Ca
2+
sensors. The extracellular Ca concen-
2+
1 opening in the cell membrane is increased by provides a much clearer message than the
! Ligands (e.g., via G o proteins; ! p. 274);
2+
! Intracellular messengers (e.g., IP 3 and cAMP; tration [Ca ] o plays an important role in blood
! p. 274ff.); coagulation and bone formation as well as in
2+
! Stretching or heating of the cell membrane. nerve and muscle excitation. [Ca ] o is tightly
The Ca channels of the endoplasmic and sar- controlled by hormones such as PTH, calcitriol
2+
coplasmic reticulum open more frequently in and calcitonin (! p. 290), and represents the
2+
response to signals such as a rise in [Ca ] i (in- feedback signal in this control circuit
2+
flux of external Ca 2+ works as the “spark” or (! p. 290). The involved Ca sensors are mem-
trigger) or inositol tris-phosphate (IP 3; ! A2 brane proteins that detect high [Ca ] o levels
2+
and p. 276). on the cell surface and dispatch IP 3 and DAG
2+
A rise in [Ca ] i is a signal for many impor- (diacylglycerol) as intracellular second mes-
tant cell functions (! A), including myocyte sengers with the aid of a G q protein (! C1 and
2+
contraction, exocytosis of neurotransmitters p. 274ff.). IP 3 triggers an increase in the [Ca ] i
in presynaptic nerve endings, endocrine and of parafollicular C cells of the thyroid gland.
exocrine hormone secretion, the excitation of This induces the exocytosis of calcitonin, a
certain sensory cells, the closure of gap junc- substance that reduces [Ca ] o (! C2). In para-
2+
2+
tions in various cells (! p. 19 C), the opening thyroid cells, on the other hand, a high [Ca ] o
of other types of ion channels, and the migra- reduces the secretion of PTH, a hormone that
2+
tion of leukocytes and tumor cells ( ! p. 30) as increases the [Ca ] o. This activity is mediated
well as thrombocyte activation and sperm mo- by DAG and PKC (protein kinase C) and, per-
bilization. Some of these activities are medi- haps, by a (G i protein-mediated; ! p. 274) re-
ated by calmodulin. A calmodulin molecule duction in the cAMP concentration (! C3).
2+
2+
can bind up to 4 Ca ions when the [Ca ] i rises Ca 2+ sensors are also located on osteoclasts as
2+
(! A2). The Ca -calmodulin complexes acti- well as on renal and intestinal epithelial cells.
vate a number of different enzymes, including
calmodulin-dependent protein kinase II (CaM-
kinase II) and myosin light chain kinase
(MLCK), which is involved in smooth muscle
36 contraction (! p. 70).
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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