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An overview of the potassium channel family.
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2. ASHCROFT, F.M.
Voltage-gated K+ channels.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.97-123.
3. SANSOM, M.S.
Putting the parts together.
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5. TKATCH, T., BARANAUSKAS, G. AND SURMEIER, J.
K+ Current amplitude are linearly related in basal ganglia and basal
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The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated
protein kinase ERK.
J.NEUROCHEM. 75(6) 2277-87 (2000).
Potassium ion (K+) channels are a structurally diverse group of proteins
that facilitate the flow of K+ ions across cell membranes. They are
ubiquitous, being present in virtually all cell types. Activation of K+
channels tends to hyperpolarise cells, reducing the membrane's electrical
resistance, dampening nervous activity. In eukaryotic cells, K+ channels are
involved in neural signalling and generation of the cardiac rhythm, and
act as effectors in signal transduction pathways involving G protein-
coupled receptors (GPCRs). In prokaryotic cells, they play a role in the
maintenance of ionic homeostasis .
Structurally, Kv channels belong to the subfamily of K+ channels whose
subunits contain 6 transmembrane (TM) domains: these are the voltage-
gated K+ (Kv) channels, the KCNQ channels, the EAG-like K+ channels and
3 kinds of Ca2+-activated K+ channels (BK, IK and SK) . All K+
channels share a characteristic sequence feature: a TMxTVGYG motif
that resides between the 2 C-terminal membrane spanning helices, and
forms the K+-selective pore domain [1-2].
The Kv family can be divided into 4 subfamilies on the basis of sequence
similarity and function: Shaker (Kv1), Shab (Kv2), Shaw (Kv3) and Shal
(Kv4). All consist of pore-forming alpha subunits that associate with
different types of beta subunit. To form a functional K+ channel pore,
4 alpha subunits and 4 beta subunits are required. The alpha subunits
have 6 well-conserved TM domains, a pore loop region and variable length
N- and C-termini. TM domains 5 and 6, and the loop region, form the K+
channel pore through which the K+ ions pass .
The first Shal (Kv4) sequence was found in Drosophila. Several vertebrate
K+ channels with similar amino acid sequences were subsequently found and,
together with the Drosophila Shal channel, now constitute the Shal (Kv4)
family. These channels support outward K+-selective currents and are
inhibited by free fatty acids . The Shal family can be further divided
into 3 families, designated Kv4.1, Kv4.2 and Kv4.3.
Kv4.2 channels are the major contributors to somatodendritic A-type K+
channels in the basal ganglia and basal forebrain neurons . They are also
expressed in the heart and CNS. In rodents, they are an important
constituent of the cardiac transient outward current, Ito. In addition, they
have a predicted role in regulating neuronal transmission at post-synaptic
loci in defined brain regions [4-5]. Kv4.2 channels contain a number of
conserved sites for mitogen-activated protein kinase ERK phosphorylation,
suggesting that ERK may regulate potassium channel function by direct
KV42CHANNEL is a 5-element fingerprint that provides a signature for the
Kv4.2 voltage-gated K+ channel. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise the Kv4.2 channels but distinguish them from other
members of the Shal family - motifs 1 and 2 reside at the N-terminus; and
motifs 3-5 span the C-terminus. Two iterations on SPTR39_15f were required
to reach convergence, at which point a true set comprising 5 sequences was
identified. Two partial matches were also found, Q99249 and Q9JJ60, both of
which are closely related K+ channel proteins that match motifs 1-3.