Biomedical Engineering Reference
In-Depth Information
Tabl e 8. 3.
Calcium signals regulated directly or indirectly by IP
3
Rs in smooth myocytes
(Source: [
717
]; Ca
V
: voltage-dependent Ca
2
+
channel; NEx: Na
+
-Ca
2
+
exchanger; NSCC: non-
selective cation channel; RyR: ryanodine-sensitive Ca
2
+
release channel; SOC: store-operated
Ca
2
+
channel; TRPC: transient receptor potential canonical channel; TRPM: melastatin-related
transient receptor potential channel).
Calcium
Frequency
Rise
Decay
Spatial
Involved
Ca
2
+
signals
(Hz)
time
half-time
spread
(s)
(s)
(
m)
channels
Flash
0.2-0.5
0.2-0.8
0.5-1.5
Ca
V
,RyR
Global
Ca
V
, NSCC,
spread
RyR, SOC
TRPC1/3,
TRPM4
Oscillation
0.07-0.4
2-6
3-18
RyR,
TRPC6
Puff
0.02-0.04
0.06-0.16
0.11-0.25
1.89-2.51
RyR
Ripple
0.05-0.19
1-2
4-6
Spark
0.07-0.59
0.01-0.07
0.03-0.15
0.52-4.7
RyR
Wave
0.04-1.41
0.5-2
2-10
8.8-50
Ca
V
,
NSCC, NEx,
RyR, SOC
Plasmalemmal Gq/11-coupled receptors stimulate phospholipase-C that
hydrolyzes plasmalemmal phosphatidylinositol (4,5)-bisphosphate and generates
diacylglycerol and inositol (1,4,5)-trisphosphate.
Inositol trisphosphate receptors constitute a set of tetrameric intracellular Ca
2
+
release channels on the endoplasmic reticulum membrane that generate Ca
2
+
signals (Vol. 3 - Chap. 3. Main Classes of Ion Channels and Pumps). Three
IP
3
R isoforms (IP
3
R1-IP
3
R3; Table
8.4
) encoded by distinct genes are responsible
for signaling differences with given frequencies, amplitudes, and spatiotemporal
properties. These 3 isoforms are synthesized in smooth myocytes. Subtype IP
3
R1 is
the predominant isoform in vascular smooth myocytes; IP
3
R2 and IP
3
R3 densities
are higher in proliferating vascular smooth myocytes [
717
]. In the tracheal smooth
muscle, IP
3
R3 is the principal isoform, IP
3
R1 and IP
3
R2 being also expressed [
717
].
The cytosolic N-terminus possesses an IP
3
-binding domain, a suppressor motif
that inhibits IP
3
binding, and a regulatory sequence with binding sites for ATP and
Ca
2
+
ion as well as phosphorylation sites and a coupling region for interacting with
transient receptor potential canonical (TRPC) channels [
717
]. The transmembrane
region and cytosolic C-terminus enable IP
3
R tetramerization.
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