Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). For example Kv1 (homologous to Drosophila Shaker), Kv2 (Shab), Kv3 (Shaw), Kv4 (Shal), Kv5, Kv6, , Kv8 and the other Kv channels listed in Channelpedia.
Outward rectifiers constitute a large class of voltage-dependent K+ channels.
They have six transmembrane domains (S1–S6), one very positively charged (S4), and a typical pore region situated between
S5 and S6 ,, , . Sequence similarities between members of the
Kv family were initially used to define the different subfamilies of alpha subunits. The different members within a given subfamily
share only a percentage of 30 –50% with members of others
subfamilies. To date 20 functional voltage-gated potassium
channels alpha subunits have been described. They belong to six
subfamilies designated Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw),
Kv4 (Shal), KvLQT, and EAG. The diversity of potassium channel functions comes from the diversity of potassium channel genes and is increased by alternate
splicing (10, 11), regulatory beta subunits (12–14) and heteromultimerization between the different alpha subunits of the same subfamily , , , or sometimes between different subfamilies
: Potassium channel
The following is paraphrased from : Kv channels are composed of four
subunits that surround the central ion permeation pathway.
Each subunit has six transmembrane domains (S1–S6) and a
pore region containing the signature sequence GYG characteristic for potassium channels , . Post-translational assembly of
tetrameric Kv channels takes place in the ER2 membrane; sub-
sequently the channels traffic to the plasma membrane , . A
highly conserved sequence in the cytoplasmic N terminus of Kv
channels, the tetramerization domain or T1 domain, has been
shown to play an important role in channel assembly , . The
T1 domain contains some of the molecular determinants for
subfamily-specific homo- or heterotetrameric assembly of Kv
alpha-subunits , ,, . The most striking difference between the
T1 domains of Kv1 (Shaker) and Kv2–4 (non-Shaker) channels
is the presence of intersubunit-coordinated Zn2+ ions at the
assembly interface in non-Shaker channels. The Zn2+ ions are
coordinated by a C3H1 motif embedded in a conserved
sequence motif (HX5CX20CC) of the T1 domain, which is
located near the distal end of the N terminus , , . These
four amino acids are exposed on the subunit interface, with one
histidine and two cysteine residues belonging to one subunit
and one cysteine residue belonging to the neighboring subunit
. The T1 domain facilitates tetrameric assembly of Kv channels. Kv subunits in which the T1 has been deleted have been
reported to assemble in a promiscuous way via their transmembrane domains and to form stable, functional channels, but
both the rates and the efficiency of channel assembly are significantly lower in the mutant channels as compared with their
wild-type counterparts , . Heteromeric assembly of channel subunits is a potential source of diversity of K+ channel
Eight different voltage-gated K+ (Kv)3 Shaker-related channel subfamilies (Kv1–Kv6 and Kv8–Kv9) have been identified based on the degree of sequence homology . Fully assembled Kv channels are composed of four α-subunits arranged around a central pore. Each α-subunit consists of six transmembrane segments S1–S6 with a cytoplasmic N and C terminus. The N terminus contains the T1 domain, a tetramerization domain that facilitates the assembly of α-subunits into functional channels. The presence of a T1 domain is not absolutely required for channel assembly because subunits without a T1 domain could also assemble into a functional tetramer, although less efficiently , , . However, the T1 domain not only promotes but also restricts the formation of possible homo- and heterotetramers by preventing incompatible subunits from assembling , . When four compatible T1 domains assemble, they are arranged with the same 4-fold symmetry as the transmembrane segments, forming a hanging gondola structure .
Voltage-gated potassium channels of the Kv family are
strongly expressed in the mammalian central nervous system,
in the immune system, in muscle cells and in many other cell
types. Most neurons express multiple Kv channel subtypes belonging to one
or more subfamilies , , .
Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume.
Voltage gated potassium channels play a key role in controlling neuronal
excitability and regulate a variety of electrophysiological properties, such as the interspike membrane potential, the waveform of the action potential and the firing frequency .