Biomedical Engineering Reference
In-Depth Information
IK
r
Delayed rectifier potassium current
IND
Investigational new drug approval
K
+
Potassium
K
v
Voltage-gated Potassium channel
K
v
11.1
hERG
Potassium channels
LQTS
Long QT syndrome
NCE
New chemical entity
PD
Pharmacodynamic
PK
Pharmacokinetic
QTc
QT interval correction
Rb
+
Rubidium
Sarcoplasmic ER Ca
2+
-ATPase
SERCA
Tdp
Torsade de pointes
TEA
+
Tetraethyl ammonium
TMO
Trimethyl amineoxide
VSD
Voltage sensing domain
WT
Wild type
1
Introduction
Potassium (K
+
) channels are the most widely distributed type of ion channel and are
found in virtually all living organisms. They have been considered to be the third
largest group of the signaling molecule after protein kinase and G-protein-coupled
receptors. K
+
channels control the membrane potential (frequency and shape of
action potential), secretion of hormones (insulin secretion from
cells of pancreas)
and neurotransmitters by altering the excitability. Their activity may be regulated
by different voltage-gated ions (sodium and calcium), neurotransmitters and differ-
ent signaling pathways stimulated by potassium ions. K
+
channels have been
characterized and classified into four structural types based on their activation
and their transmembrane domains (TMs): (a) Ca
2+
-activated K
+
channels (K
ca
)
having 6 or 7 TM in each
b
-subunit and open in response to the presence of calcium
ions or other signaling molecules, (b) inwardly rectifying potassium channel (K
ir
)
having 2 TM and passes current (positive charge) more easily in the inward
direction, (c) Tandem pore domain potassium channel (K
2P
) having 4 TM and
2 pores and are constitutively open and possess high basal activation and (d)
Voltage-gated potassium channel (K
v
) having 6 TM and open or close in response
to changes in transmembrane voltage (for details, please see flowchart).
Voltage-gated potassium channel (K
v
) in human is encoded by 40 genes and
divided into 12 subfamilies. K
v
channel was first cloned in drosophila shaker
channel. All mammalian K
v
channels consist of four
a
-subunits, each containing
a
six transmembrane
-helical segments, S1-S6 and a membrane-reentering P-loop,
which are arranged circumferentially around a central pore as homotetramers or
heterotetramers (Fig.
1
). This ion conduction pore is lined by four S5-P-S6
a
