Biomedical Engineering Reference
In-Depth Information
i
K1
,
i
K
AT P
,and
i
K
ACh
currents, respectively (Vol. 3 - Chap. 3. Main Classes of Ion
Channels and Pumps). They conduct substantial current near the resting potential,
but carry little or no ions at depolarized potentials [
466
].
The second group of K
+
channel subunits contains 6 transmembrane segments
(S1-S6; 6TM and 1P class [K
6TM1P
]). The S5-P-S6 region resembles the 2TM-
1P subunit. The additional membrane-spanning segments, especially the charged
S4 segment, yield voltage-dependent gating (K
V
channels). They are closed at
resting potential, but activate at different rates upon depolarization to drive transient
outward and several sustained delayed rectifying currents that control the duration
of action potentials [
466
].
Various subunits of different K
V
subfamilies are sources of functioning diversity
in cardiac cells (nodal cells and cardiomyocytes). A special set of K
6TM1P
subunits
is responsible for the pacemaker current, as they activate upon hyperpolarization.
They carry both Na
+
and K
+
ions.
Channel subunits of both K
2TM1P
and K
6TM1P
classes assemble into homo- or
heterotetrameric channels. In addition, concatenation of 2 K
2TM1P
subunits
([K
2TM1P
]
2
) form members of the K
4TM2P
class. These dimers yield voltage-
independent leak channels [
466
].
5.10.4.1
Voltage-Gated Potassium Channels (K
V
)
Voltage-gated potassium channels are characterized by a functional diversity
relevant to action potential repolarization in the myocardium. Multiple cardiac
voltage-gated K
+
currents contribute to variations in shape of action potentials in
different regions of the myocardium (Sect.
6.5
) and control of cardiac excitability.
Voltage-gated K
+
channels are targeted by various endogenous neurotransmitters
and neurohormones as well as exogenous drugs to modulate cardiac functioning.
Myocardial voltage-gated potassium channels are made of several subunit sets:
K
V
1(K
V
1.1-K
V
1.8); K
V
2(K
V
2.1 and K
V
2.2); K
V
3(K
V
3.1-K
V
3.4); K
V
4(K
V
4.1-
K
V
4.3); K
V
5; K
V
6; K
V
7; and K
V
11.1 [
469
]. Functional voltage-gated K
+
channels
comprise 4 subunits. Members of this channel family combine various kinds of
subunits with different time and voltage-dependent properties.
Retrograde microtubule-dependent transport modulates surface expression of
several potassium channels in ventricular myocytes. The number of K
V
2.1, K
V
3.1,
K
V
4.2, K
V
11.1, and K
IR
2.1 increases when dynein is inhibited [
470
].
In adult mouse ventriculomyocytes, 4 kinetically and pharmacologically distinct
voltage-gated K
+
currents exist [
472
]: (1) a rapidly activating and inactivating,
transient outward K
+
current (
i
K
,
to
(
r
)
) through K
V
4 channel; (2) a rapidly activating,
slowly inactivating, transient outward K
+
current (
i
K
,
to
(
s
)
) through K
V
1.4 channel;
(3) a rapidly activating, very slowly inactivating K
+
current (
i
K
,
slow
) through
K
V
1.5 channel; and (4) a slowly activating, non-inactivating K
+
current (
i
K
,
ss
).
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