Biomedical Engineering Reference
In-Depth Information
Table 5.13.
Activation and inactivation rates of voltage-gated potassium channels (from [
471
]).
There are more transient outward K
+
channels in epicardium than in endocardium, and in right
than in left ventricle epicardium.
K
+
channel
Activation
Inactivation
Fast transient outward
Fast
Fast
Slow transient outward
Fast
Slow
Ultrarapid delayed rectifier
Fast
No
Rapid delayed rectifier
Moderate
Fast
Slow delayed rectifier
Very slow
No
The 2 last current types are detected in all ventriculomyocyte types, but not the
2 first types (either
i
K
,
to
(
r
)
in ventriculomyocytes isolated from the apex or
i
K
,
to
(
s
)
)
in ventriculomyocytes isolated from the septum) [
472
]. In ferret left ventricular
epicardial and endocardial myocytes, transient outward K
+
currents results from
activity of K
V
4.2 and K
V
4.3 (epicardial
i
K
,
to
(
r
)
)andK
V
1.4 (endocardial
i
K
,
to
(
s
)
),
respectively [
473
].
In mice, a truncated K
V
1.1 protein attenuates the slow inactivating outward K
+
current (
i
K
,
to
(
s
)
), thereby increasing action potential duration and QT interval on
electrocardiogram traces and causing spontaneous ventricular arrhythmias [
474
].
AK
V
4.2 pore mutant eliminates the rapidly inactivating transient outward current
(
i
K
,
to
(
r
)
), thus markedly prolonging action potential duration, without generating
arrhythmias [
474
]. The higher the prolongation of action potential duration and QT
interval, the lower the risk of spontaneous ventricular arrhythmias.
Transient Outward K
+
Currents
Transient outward K
+
channels set the rate of the early phase of repolarization.
They are quickly inactivated (Table
5.13
). Two subtypes can be identified, fast and
slow, according to the rates of inactivation and recovery from inactivation. Rapidly
and slowly inactivating transient outward K
+
currents are associated with K
V
4
α
subunits and K
V
1.4, respectively.
Atrial, rapidly inactivating, transient outward K
+
current (
i
K
,
to
(
r
)
) through K
V
4.3
contributes to phase-1 rapid repolarization of cardiac action potentials. Current
i
K
,
to
(
r
)
varies according to the intramural location (endocardium, midmyocardium,
and epicardium) of ventriculomyocytes of the human heart.
Rapidly inactivating transient outward heterotetrameric K
+
channels are made
of: (1) pore-forming
α
subunits, i.e., K
V
4.2 and predominant K
V
4.3; (2) accessory
β
subunits, i.e., K
V
channel-interacting protein KChIP2; and (3) the high-affinity,
Search WWH ::
Custom Search