Biomedical Engineering Reference
In-Depth Information
low-capacity, calcium-binding, calcium sensor, frequenin homolog, or neuronal
calcium sensor NCS1 [
469
].
93
Transcription factor Irx5 from the Iroquois homeobox genes controls the action
potential. It represses expression of the KCND2 gene that encodes K
V
4.2 sub-
unit of voltage-gated potassium channel via the recruitment of muscle-restricted,
histone deacetylase-dependent transcriptional repressor, SET and MYND domain-
containing protein SMYD1, or zinc finger protein BOp (for CD8b opposite; also
called ZMYND18) [
475
].
94
Protein Irx5 (but neither Irx3 nor Irx4) increases K
V
4.2
promoter activity in cardiac fibroblasts,
95
whereas it decreases K
V
4.2 promoter
activity in ventricular myocytes [
476
]. Transmural gradient of
i
Kto
current density
across the left ventricular wall results from difference in transcription factors that
control the KCND2 and KCNIP2 genes that encode K
V
4.2 or KChIP2 according to
mammalian species.
96
Activity of human atrial K
V
4.3 channel is modulated by [
477
]: (1) plasmalemmal
epidermal growth factor receptor (EGFR) protein Tyr kinase (phosphorylation
of Tyr136) and (2) cytosolic SRC family kinases (phosphorylation of Tyr108).
Phosphatase PP2, an inhibitor of SRC family of protein Tyr kinase markedly reduces
K
V
4.3 current.
97
Various molecules also regulate the cardiac transient outward potassium current
[
477
].
-Adrenergic receptor hinders
i
K
,
to
(
r
)
in rabbit ventriculomyocytes. In hu-
man cardiomyocytes, protein kinase-C reduces
i
K
,
to
(
r
)
α
current. Activated Ca
2
+
-
calmodulin-dependent protein kinase CamK2 slows K
V
4.3 inactivation and accel-
erates the recovery rate from inactivation. Nitric oxide inhibits human atrial K
V
4.3
channel; adenylate cyclase activates PKA kinase and PP2 phosphatase.
93
Frequenin binds to many protein types (either in a calcium-dependent or -independent fashion),
such as protein phosphatase-2, phosphatidylinositol 4-kinase-3
), phosphodiesterases,
nitric oxide synthase, adpribosylation factor ARF1, IP
3
receptor, K
V
4.3 channel, TRPC5 channel,
G-protein-coupled receptor kinase GRK2, dopamine D
2
receptor, and interleukin-1 receptor
accessory protein-like protein (IL1RAPL).
94
Protein SMYD1 intervenes in cardiomyocyte differentiation and cardiac morphogenesis. The
BOP alias is also used for Eye absent homolog EyA1 of cardiac and skeletal myocytes that
can act as a transcriptional activator. Mutations in the EYA1 gene cause autosomal dominant
type-1 branchio-oto-renal (BOR1) dysplasia syndrome, type-1 branchio-otic syndrome (BOS1),
congenital cataracts, and ocular anterior segment anomalies. These syndromes constitute branchio-
oto-renal spectrum disorders.
95
Protein Irx4 inhibits Irx5-induced increase in channel promoter activity in fibroblasts.
96
Transmural gradient is caused by expression gradient of K
V
4.2 and/or K
V
4.3 in small mammals
and KChIP2 subunits in large mammals.
97
Protein Tyr kinases modulate activity of many ion channels, such as Ca
V
1.2, Na
V
,andvolume-
sensitive Cl
−
channels in cardiomyocytes, in addition to several types of K
+
channels in different
cell types and TRPC channels. Cardiac volume-sensitive Cl
−
,Na
V
,andK
V
11.1 are regulated by
both EGFR and SRC family kinases. Cardiac K
V
7.1, K
IR
2.1, and K
IR
2.3 are controlled by EGFR
kinase.
β
(PI4K3
β
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