Biomedical Engineering Reference
In-Depth Information
usually closed at the resting potential of the cell, and opened on membrane
depolarization, and are involved in the repolarization of the action potential and
thus the electrical excitability of cardiac myocytes.
2 Biological Characterization of Potassium Channel Subtypes
That Involved in Arrhythmic Diseases
The first crystallographic data of potassium channels was resolved on bacterial
KcsA
channel reported by R. MacKinnon who was honored for Nobel Prize in
the year 2005 [
6
]. After that, the three-dimensional structures of calcium-activated
potassium channel
MthK
[
7
], inwardly rectifying potassium channels
K
ir
Bac
[
8
],
and voltage-gated potassium channels
K
v
AP
[
9
] and
K
v
1.2
[
10
] have been reported.
To our knowledge,
K
v
1
(
shaker
) family channels have been extensively studied
for their biological characteristics and electrophysiological features since they
could be easily expressed in tool cells such as Chinese Hamster Ovary (CHO)
or Human Embryonic Kidney (HEK). Taking
K
v
1.2
potassium channel as an
example, mammalian
K
v
channels could be divided into three parts: extracellular
region, membrane region, and cytoplasm region. In the extracellular and membrane
region,
K
v
channels are assembled by the interactions of four identical or distinct
a
-subunits, which constituted to the pore forming of the channel. The cytoplasm
region contains an auxiliary
-subunit that modified the functions of the pore-
b
forming
-subunits as well as the T
1
auxiliary region, SH
3
binding domain, ball
peptide, and other functional domain [
11
]. In
shaker
family
K
v
channel, one
a
a
subunit contains three parts. The core region is constituted of six transmembrane
domains (6-TM) that coded by S1 to S6 in which S4 helix possess positive charges
that is related to the gating actions. The other two parts is the N terminus and the C
terminus. Among the 6-TM, the pore-forming region (P-region) located between
S5 and S6 helix possesses a specific selectivity filter amino acid sequence
(TVGYG) to form the potassium ion permeation pathway. Recently, the common
structural features for the P-region in the
shaker
family
K
v
channels were
summarized: First, the selectivity filter of the channel protein on the extracellular
side of the pore is relatively conserved, while the inner pore between the selec-
tivity filter and intracellular solution varies in its conformation [
6
,
9
,
10
,
12
-
14
];
Besides, a highly conserved Pro-X-Pro triplet peptide sequence acts as the deter-
minate factor for gating in
shaker
family
K
v
channels [
15
,
16
]. It was concluded
that the structural conservation of the selectivity filter underlies the conserved
mechanism of selective ion conduction in potassium channels, while the variation
of the inner pore structure relies on conformational changes between open- and
close-state illustrates the structural diversities of potassium channels blockers
(Fig.
1
).
