Biomedical Engineering Reference
In-Depth Information
rafts and caveolae. Channel Ca
V
1.2 assembles with
2-adrenoceptor, Gs subunit of
G protein, adenylate cyclase, AKAP, PKA, phosphatase PP2, and caveolin-3 [
339
].
Protein kinase-A as well as calmodulin-dependent protein kinase CamK2 phos-
phorylate Na
V
1.5 and Ca
V
1.2 channels, ryanodine-sensitive Ca
2
+
-release channel
RyR2,
4
β
and phospholamban regulator of sarco(endo)plamic reticulum calcium
AT P a s e .
Disc large homolog DLg4 is required for K
V
1.4 localization in membrane
rafts [
339
]. In the atrial myocardium, K
V
1.5 channels lodge in intercalated discs
that lack caveolin-3. Disc large homolog DLg1 that binds to cadherin promotes
K
V
1.5 localization in membrane rafts. In intercalated discs, connexin-43 resides in
membrane rafts, where it links to N-cadherin.
Channel K
IR
2 complexes with DLg1 and DLg4 adaptors [
339
]. In membrane
rafts, DLg1 and DLg4 tether other scaffold proteins, such as calcium-calmodulin-
dependent protein Ser kinase (CASK) of the membrane-associated guanylate kinase
(MAGUK) family, vertebrate Lin7 homolog VeLi1, and Munc18-1-interacting
protein MInt1
5
to form a complex that recruits K
IR
2 to the plasma membrane [
339
].
Both DLg1 and DLg4 connect also to Ca
2
+
-activated calmodulin-dependent
kinase CamK2 that regulates numerous ion channels according to intracellular Ca
2
+
concentration. Most channels regulated by CamK2 localize in membrane rafts and
caveolae with CamK2, such as Ca
V
1.2, K
V
1.5, IP
3
R, and Na
+
channels [
339
].
In addition, DLg1 and DLg4 link to A-kinase anchoring proteins. Channel K
V
7.1
associates with both PKA and PP1phosphatase via AKAP9 [
339
]. The AKAP
proteins interact also with
2-adrenoceptors. Therefore, channelosomes can be
controlled by the sympathetic system.
Like
β
β
-adrenergic receptor and its G protein, adenylate cyclase, and protein
kinase-A,
α
1 adrenergic receptor, caveolin-3, Gq subunit of G protein, and phospho-
lipase C
3) are confined to caveolae [
340
]. A decrease
in caveolin-3 density may contribute to the development of cardiac maladaptive
hypertrophy.
β
subtypes (PLC
β
1andPLC
β
5.2.2
Sarcoplasmic Reticulum
The sarcoplasmic reticulum is a smooth endoplasmic reticulum in myocytes.
Whereas the endoplasmic reticulum synthesizes molecules, the sarcoplasmic reticu-
lum stores, pumps, and expels calcium ions. The sarcoplasmic reticulum sequesters
a large amount of calcium that can be released on the arrival of the action
potential owing to special connections between the sarcoplasmic reticulum and the
sarcolemma with T-tubules.
4
Ryanodine receptor is a sarcoplasmic reticulum Ca
2
+
channel that is able to bind to ryanodine.
5
A.k.a. adaptor X11
α
.
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