Biomedical Engineering Reference
In-Depth Information
Tabl e 5. 1.
Ion channels in caveolae and membrane rafts of the sarcolemma of nodal cells and
cardiomyocytes (Source: [
339
]). Among hyperpolarization-activated and cyclic nucleotide-gated
(HCN) channels, HCN4 is the main isoform in the sinoatrial node; HCN1 and HCN2 are also
synthesized.
Channel
Membrane localization
Ca
V
1.2
Caveolae
IP
3
R
Caveolae
K
V
1.4
Membrane raft
K
V
1.5
Caveolae (ventriculomyocyte)
Membrane raft (atriomyocyte)
K
V
2.1
Membrane raft
K
V
4.2
Membrane raft
K
IR
2.1
Membrane raft
K
IR
3.1
Membrane raft
K
IR
6.1
Membrane raft
K
IR
6.2
Membrane raft
K
Ca
Membrane raft
Na
V
1.5
Caveolae (ventriculomyocyte)
HCN4
Caveolae (nodal cell of sinusal node)
the cell center via a Ca
2
+
release from the sarcoplamic reticulum. This lattice
becomes active and allows a centipetal diffusion of Ca
2
+
ions when a greater atrial
contraction is required.
5.2.1.3
Plasmalemmal Nanodomains
Membrane rafts and caveolae (50-100 nm plasmalemmal invaginations) constitute
dynamic platforms that recruit ion channels and their partners to build channelo-
somes. Certain cardiac channel subunits that shape the cardiac action potential
(Sect.
5.10
) actually localize to membrane rafts and/or caveolae, such as those of
Ca
V
1.2, K
AT P
K
IR
6.2), K
IR
2, K
IR
3, K
V
1.4, K
V
1.5, K
V
2.1, and Na
V
1.5 (Table
5.1
)
[
339
]. Ion channel partners, receptors of nervous control, and protein kinases and
phosphatases that coreside in channelosomes modulate localization and/or activity
of ion channels.
Caveolin-3 associates with dystrophin and
β
-dystroglycan that are components
of the dystrophin-associated protein complex. Dystrophin and
α
-actinin anchor
caveolae to the actin cytoskeleton [
339
]. Sodium channels that localize in cardiomy-
ocyte T-tubular caveolae interact specifically with syntrophin, another constituent of
the DAPC complex [
339
].
The cAMP-dependent regulation of voltage-gated calcium channels Ca
V
1.2
relies on interaction between A-kinase anchoring proteins and protein kinase-A.
A-kinase anchoring proteins recruit protein kinase-A near ion channels in membrane
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