Biomedical Engineering Reference
In-Depth Information
Abbreviations
AERP
Atrial effective refractory period
APD
Action potential duration
CHO
Chinese hamster ovary
ERP
Effective refractory period
HEK
Human embryonic kidney
I
Kr
Rapid delayed rectifier potassium channel currents
I
Kur
Ultrarapid delayed rectifier potassium current
IUPHAR
International union of basic and clinical pharmacology
TdP
Torsades de pointes
VERP
Ventricular effective refractory period
1
Introduction
Potassium channels, encoded by more than eighty genes, are one of the most
diverse classes of cell membrane proteins that modulate cell membrane potential
and excitability. Potassium channels are responsible for various neurological, car-
diovascular, and other physiological processes. According to the International
Union of Basic and Clinical Pharmacology (IUPHAR) criteria, potassium channels
can be divided into four superfamilies, including voltage-gated potassium channels
(
K
v
)[
1
], calcium-activated potassium channels (
K
Ca
)[
2
], inwardly rectifying
potassium channels (
K
ir
)[
3
], and two-pore domain potassium channels (
K
2P
)[
4
].
The structures for the four potassium channel superfamilies are distinct.
K
v
and
K
Ca
channel families often possess six transmembrane domains (6-TM) and could
be further subdivided into several conserved gene families.
K
v
channels are com-
posed of
K
v
1
,
K
v
2
,
K
v
3
and
K
v
4
subunits that corresponding to four genes named
Shaker
,
Shab
,
Shaw
, and
Shal
, respectively, the silent
K
v
5,
K
v
6
,
K
v
8
,
K
v
9
subunits,
namely KCNQ channels (
K
v
7
), as well as the eag-like (
K
v
10-K
v
12
) subunits [
5
],
while
K
Ca
channels are designated into
BK
Ca
,
IK
Ca
, and
SK
Ca
subfamilies [
2
].
K
ir
channels contain four transmembrane regions (4-TM) that possess the property of
inward rectification, which was evoked by hyperpolarizations from the potassium
equilibrium potential and was responsible for the membrane potential and the
potassium ion transportation across membranes [
3
]. The
K
2P
channel family is
structurally distinct in which each subunit contains two pore-forming domains and
four transmembrane segments.
K
2P
channels could be modulated by many physio-
logical and chemical factors, and play a crucial role in setting the resting membrane
potential and regulating cell excitability [
4
].
Among the four superfamilies potassium channels, voltage-gated potassium
channels (
K
v
) expressed in both excitable cells and nonexcitable cells play key
roles in the maintenance of cell action potential in cardiac myocytes. They are
