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K

Description: Potassium channel

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Introduction

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 [737],[738], [739], [740]. 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 [741], [733], [734], or sometimes between different subfamilies [742], [743].


Experimental data


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Gene


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Transcript


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Ontology


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Interaction


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Protein


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Structure

The following is paraphrased from [664]: 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 [667], [619]. Post-translational assembly of tetrameric Kv channels takes place in the ER2 membrane; sub- sequently the channels traffic to the plasma membrane [619], [668]. 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 [619], [669]. The T1 domain contains some of the molecular determinants for subfamily-specific homo- or heterotetrameric assembly of Kv alpha-subunits [669], [660],[598], [670]. 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 [671], [672], [673]. 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 [671]. 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 [668], [674]. Heteromeric assembly of channel subunits is a potential source of diversity of K+ channel properties.

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 [606]. 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 [677], [678], [679]. However, the T1 domain not only promotes but also restricts the formation of possible homo- and heterotetramers by preventing incompatible subunits from assembling [680], [660]. When four compatible T1 domains assemble, they are arranged with the same 4-fold symmetry as the transmembrane segments, forming a hanging gondola structure [681].


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Distribution


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Expression

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 [496], [638], [665].


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Functional

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 [666].


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Kinetics


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Model

[1] HHK (Model ID = 1)

AnimalSquid
CellType giant Axon
Age 0 Days
Temperature9.3°C
Reversal -78.0 mV
Ion K +
Ligand ion
Reference A L Hodgkin et. al; Bull. Math. Biol. 1990
mpower 4.0
mAlpha (0.01*(10-v))/(exp((10-v)/10) - 1.0) If v neq 10
mBeta 0.125 * (exp(-v/80))
28

MOD - xml - channelML

[2] KSlow (Model ID = 30)

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
mInf (1/(1 + exp(-(v+14)/14.6)))
mTau (1.25+175.03*exp(-v * -0.026)) If v lt -50
mTau (1.25+13*exp(-v*0.026)) If v gteq -50
hpower 1.0
hInf 1/(1 + exp(-(v+54)/-11))
hTau 360+(1010+24*(v+55))*exp(-((v+75)/48)^2)
118

MOD - xml - channelML

[3] KSlow_S (Model ID = 31)

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
mInf (1/(1 + exp(-((v-21)+14)/14.6)))
mTau (1.25+175.03*exp(-(v-21) * -0.026)) If v lt -29
mTau (1.25+13*exp(-(v-21)*0.026)) If v gteq -29
hpower 1.0
hInf 1/(1 + exp(-((v-21)+54)/-11))
hTau 360+(1010+24*((v-21)+55))*exp(-(((v-21)+75)/48)^2)
121

MOD - xml - channelML

[4] Kfast (Model ID = 32)

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 1.0
mInf 1/(1 + exp(-(v+47)/29))
mTau (0.34+0.92*exp(-((v+71)/59)^2))
hpower 1.0
hInf 1/(1 + exp(-(v+56)/-10))
hTau (8+49*exp(-((v+73)/23)^2))
124

MOD - xml - channelML

[5] K_Pst (Model ID = 48)

[Entry not found]
Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
mInf (1/(1 + exp(-(v+1)/12)))
mTau (1.25+175.03*exp(-v * -0.026))/qt If v lt -50
mTau ((1.25+13*exp(-v*0.026)))/qt If v gteq -50
hpower 1.0
hInf 1/(1 + exp(-(v+54)/-11))
hTau (360+(1010+24*(v+55))*exp(-((v+75)/48)^2))/qt
196

[6] K_Tst (Model ID = 49)

[Entry not found]
Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -85.0 mV
Ion K +
Ligand ion
Reference A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 4.0
mInf 1/(1 + exp(-(v+0)/19))
mTau (0.34+0.92*exp(-((v+71)/59)^2))/qt
hpower 1.0
hInf 1/(1 + exp(-(v+66)/-10))
hTau (8+49*exp(-((v+73)/23)^2))/qt
199

[7] KdShu2007 (Model ID = 50)

[Entry not found]
Animalrat
CellType L5PC
Age 17 Days
Temperature23.0°C
Reversal -85.0 mV
Ion K +
Ligand ion
Reference Yousheng Shu et. al; Proc. Natl. Acad. Sci. U.S.A. 2007 Jul 3
mpower 1.0
mInf 1-1/(1+exp((v- -43)/8))
mTau 0.6
hpower 1.0
hInf 1/(1+exp((v- -67)/7.3))
hTau 1500
202


References

262

Hodgkin AL. et al. A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952.
Bull. Math. Biol., 1990 , 52 (25-71; discussion 5-23).

264

Korngreen A. et al. Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young rats: subtypes and gradients.
J. Physiol. (Lond.), 2000 Jun 15 , 525 Pt 3 (621-39).

321

Nusser Z. et al. Variability in the subcellular distribution of ion channels increases neuronal diversity.
Trends Neurosci., 2009 May , 32 (267-74).

666

Hille B. et al. Ionic selectivity of Na and K channels of nerve membranes.
Membranes, 1975 , 3 (255-323).

496

Chow A. et al. Molecular diversity of K+ channels.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (233-85).

665

Rudy B. et al. Diversity and ubiquity of K channels.
Neuroscience, 1988 Jun , 25 (729-49).

638

Jan YN. et al. Voltage-gated and inwardly rectifying potassium channels.
J. Physiol. (Lond.), 1997 Dec 1 , 505 ( Pt 2) (267-82).

669

Deutsch C. et al. Coupled tertiary folding and oligomerization of the T1 domain of Kv channels.
Neuron, 2005 Jan 20 , 45 (223-32).

670

Shen NV. et al. Deletion analysis of K+ channel assembly.
Neuron, 1993 Jul , 11 (67-76).

671

Shen NV. et al. Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
Nat. Struct. Biol., 1999 Jan , 6 (38-43).

672

Jahng AW. et al. Zinc mediates assembly of the T1 domain of the voltage-gated K channel 4.2.
J. Biol. Chem., 2002 Dec 6 , 277 (47885-90).

673

Pfaffinger PJ. et al. The role of Zn2+ in Shal voltage-gated potassium channel formation.
J. Biol. Chem., 2003 Aug 15 , 278 (31361-71).

674

Deutsch C. et al. Voltage-gated K+ channels contain multiple intersubunit association sites.
J. Biol. Chem., 1996 Aug 2 , 271 (18904-11).

679

Jan YN. et al. An artificial tetramerization domain restores efficient assembly of functional Shaker channels lacking T1.
Proc. Natl. Acad. Sci. U.S.A., 2000 Mar 28 , 97 (3591-5).

680

Philipson LH. et al. Structural determinant for assembly of mammalian K+ channels.
Biophys. J., 1994 Mar , 66 (667-73).

681

Miller C. et al. Hanging gondola structure of the T1 domain in a voltage-gated K(+) channel.
Biochemistry, 2000 Aug 29 , 39 (10347-52).

737

Pongs O. et al. Structure-function studies on the pore of potassium channels.
J. Membr. Biol., 1993 Oct , 136 (1-8).

738

Lu Z. et al. Mutations in the K+ channel signature sequence.
Biophys. J., 1994 Apr , 66 (1061-7).

739

MacKinnon R. et al. Pore loops: an emerging theme in ion channel structure.
Neuron, 1995 May , 14 (889-92).

1499

Shu Y. et al. Selective control of cortical axonal spikes by a slowly inactivating K+ current.
Proc. Natl. Acad. Sci. U.S.A., 2007 Jul 3 , 104 (11453-8).


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Contributors: Rajnish Ranjan, Michael Schartner

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