Role of Ca2+ in Cell Regulation to 4 Ca2+ ions when the [Ca2+]i rises (² A2).

Ol The V

  activate a

o .c number of different enzymes, including
0. calmodulin-dependent protein kinase II (CaM-
C kinase II) and myosin light chain kinase (MLCK),
2 2+
The cytosolic Ca + concentration, [Ca ]i, (ca. which is involved in smooth muscle
0.1 to 0.01 umol/L) is several decimal powers [Ca2+]i oscillation is characterized by multiple
2
lower than the extracellular Ca + concentration brief and regular [Ca2+]i increases (Ca2+ spikes)
[Ca2+]o (ca. 1.3 mmol/L). This is because Ca2+ is in response to certain stimuli or hormones (² B).
continuously pumped from the cytosol into The frequency, not amplitude, of [Ca2+]i
2
intracellular Ca + stores such as the oscillation is the quantitative signal for cell
endoplasmic and sarcoplasmic reticulum (² p. 17 response. When low-frequency [Ca2+]i
A), vesicles, mitochondria and nuclei (?) or is oscillation occurs, CaM-kinase II, for example, is
Ô
 Ô Ô
Ô Goth processes occur activated and phosphorylates only its target
2
by primary active transport (Ca +-ATPases) and, proteins, but is quickly and completely deacti-
in the case of efflux, by ad-ditional secondary vated (² B1, B3). High-frequency [Ca2+]i oscil-
2
active transport through Ca +/3 Na+ antiporters lation results in an increasing degree of auto-
(² A1). phosphorylation and progressively delays the
ra deactivation of the enzyme (² B3). As a result,
c the activity of the enzyme decays more and more
Ñ
slowly between [Ca2+]i signals, and each
è additional [Ca2+]i signal leads to a summation of
C enzyme activity (² B2). As with action
2
To increase the cytosolic Ca + concentration, potentials (² p. 46), this frequency-borne, digital
Ca2+ channels conduct Ca2+ from intracellular
 type of signal transmission provides a
stores and the extracellular space into the cy-tosol much clearer message than the [Ca2+]i amplitude,
(² A2). The frequency of Ca2+ channel opening which is influenced by a number offactors.
in the cell membrane is increased by  Ca2+ sensors. The extracellular Ca2+ concen-


Ôof the cell membrane (nerve and tration [Ca2+]o plays an important role in blood
muscle cells); coagulation and bone formation as well as in

(e.g., via Go proteins; ² p. 274);  nerve and muscle excitation. [Ca2+]o is tightly
Ô

 (e.g., IP3 and cAMP; controlled by hormones such as PTH, calcitriol
- p. 274ff.); and calcitonin (² p. 290), and represents the
Ô Ô 
Ôof the cell membrane. The feedback signal in this control circuit (² p. 290).
2
Ca + channels of the endoplasmic and sar- The involved Ca2+sensors are membrane proteins
coplasmic reticulum open more frequently in that detect high [Ca2+]o levels on the cell surface
2
response to signals such as a rise in [Ca +]i (influx and dispatch 1P3 and DAG (diacylglycerol) as
of external Ca2+ works as the "spark" or trigger) intracellular second messengers with the aid of a
or inositol tris-phosphate (IP3; ² A2 and p. 276). Gq protein (² C1 and p. 274ff.). IP3 triggers an
A rise in [Ca2+]i is a signal for many important increase in the [Ca2+]i of parafollicular C cells of
cell functions (² A), including myocyte the thyroid gland. This induces the exocytosis of
contraction, exocytosis of neurotransmitters in calcitonin, a substance that  [Ca2+]o (²
presynaptic nerve endings, endocrine and exocrine C2). In parathyroid cells, on the other hand, a
hormone secretion, the excitation of certain high [Ca2+]o reduces the secretion of PTH, a
sensory cells, the closure of gap junctions in hormone that increases the [Ca2+]o. This activity
various cells (² p. 19 C), the opening of other is mediated by DAG and PKC (protein kinase C)
types of ion channels, and the migration of and, perhaps, by a (Gi protein-mediated; ² p.
leukocytes and tumor cells ( ² p. 30) as well as 274) reduction in the cAMP concentration (²
thrombocyte activation and sperm mobilization. C3). Ca2+ sensors are also located on osteoclasts
Some of these activities are mediated by as well as on renal and intestinal epithelial cells.
calmodulin. A calmodulin molecule can bind up
contraction p. 70).

Despopoulos, Color Atlas of Physiology © 2003 Thieme
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c