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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].

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Structure

Kv
Visual Representation of Kv Structure
Methodology for visual representation of structure available here

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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Biophysics

Model HHK (ID=1)      

AnimalSquid
CellType giant Axon
Age 0 Days
Temperature9.3°C
Reversal -78.0 mV
Ion K +
Ligand ion
Reference [262] A L Hodgkin et. al; Bull. Math. Biol. 1990
mpower 4.0
m Alpha (0.01*(10-v))/(exp((10-v)/10) - 1.0) If v neq 10
m Beta 0.125 * (exp(-v/80))

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Model KSlow (ID=30)      

This is a better model because I think so

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference [264] A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
m Inf (1/(1 + exp(-(v+14)/14.6)))
m Tau (1.25+175.03*exp(-v * -0.026)) If v lt -50
m Tau (1.25+13*exp(-v*0.026)) If v gteq -50
hpower 1.0
h Inf 1/(1 + exp(-(v+54)/-11))
h Tau 360+(1010+24*(v+55))*exp(-((v+75)/48)^2)

MOD - xml - channelML

Model KSlow_S (ID=31)      

Modified KSlow model (V shift = -21)

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference [264] A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
m Inf (1/(1 + exp(-((v-21)+14)/14.6)))
m Tau (1.25+175.03*exp(-(v-21) * -0.026)) If v lt -29
m Tau (1.25+13*exp(-(v-21)*0.026)) If v gteq -29
hpower 1.0
h Inf 1/(1 + exp(-((v-21)+54)/-11))
h Tau 360+(1010+24*((v-21)+55))*exp(-(((v-21)+75)/48)^2)

MOD - xml - channelML

Model Kfast (ID=32)      

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference [264] A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 1.0
m Inf 1/(1 + exp(-(v+47)/29))
m Tau (0.34+0.92*exp(-((v+71)/59)^2))
hpower 1.0
h Inf 1/(1 + exp(-(v+56)/-10))
h Tau (8+49*exp(-((v+73)/23)^2))

MOD - xml - channelML

Model K_Pst (ID=48)      

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -65.0 mV
Ion K +
Ligand ion
Reference [264] A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 2.0
m Inf (1/(1 + exp(-(v+1)/12)))
m Tau (1.25+175.03*exp(-v * -0.026))/qt If v lt -50
m Tau ((1.25+13*exp(-v*0.026)))/qt If v gteq -50
hpower 1.0
h Inf 1/(1 + exp(-(v+54)/-11))
h Tau (360+(1010+24*(v+55))*exp(-((v+75)/48)^2))/qt

Model K_Tst (ID=49)      

Animalrat
CellType Neocortical L5PC
Age 15 Days
Temperature23.0°C
Reversal -85.0 mV
Ion K +
Ligand ion
Reference [264] A Korngreen et. al; J. Physiol. (Lond.) 2000 Jun 15
mpower 4.0
m Inf 1/(1 + exp(-(v+0)/19))
m Tau (0.34+0.92*exp(-((v+71)/59)^2))/qt
hpower 1.0
h Inf 1/(1 + exp(-(v+66)/-10))
h Tau (8+49*exp(-((v+73)/23)^2))/qt

Model KdShu2007 (ID=50)      

Animalrat
CellType L5PC
Age 17 Days
Temperature23.0°C
Reversal -85.0 mV
Ion K +
Ligand ion
Reference [1499] Yousheng Shu et. al; Proc. Natl. Acad. Sci. U.S.A. 2007 Jul 3
mpower 1.0
m Inf 1-1/(1+exp((v- -43)/8))
m Tau 0.6
hpower 1.0
h Inf 1/(1+exp((v- -67)/7.3))
h Tau 1500

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Expression and Distribution

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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Function

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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Interaction

Heterologous expression of homotetrameric channels of the Kv1-Kv4 subfamilies display distinctive gating characteristics associated with variations in the primary sequence. In addition, gating is known to be modified through assembly of heterotetramers consisting either of different alpha-subunits [649] or alpha-subunits with accessory beta-subunits [312].

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).

496

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

638

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

664

Mederos Y Schnitzler M et al. Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
J. Biol. Chem., 2009 Feb 13 , 284 (4695-704).

665

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

666

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

667

Barry DM et al. Myocardial potassium channels: electrophysiological and molecular diversity.
Annu. Rev. Physiol., 1996 , 58 (363-94).

668

Deutsch C Potassium channel ontogeny.
Annu. Rev. Physiol., 2002 , 64 (19-46).

669

Robinson JM 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

Bixby KA 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

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

674

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

678

Kobertz WR et al. K+ channels lacking the 'tetramerization' domain: implications for pore structure.
Nat. Struct. Biol., 1999 Dec , 6 (1122-5).

679

Zerangue N 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

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

681

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

733

Sheng M et al. Presynaptic A-current based on heteromultimeric K+ channels detected in vivo.
Nature, 1993 Sep 2 , 365 (72-5).

734

Wang H et al. Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons.
Nature, 1993 Sep 2 , 365 (75-9).

737

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

738

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

739

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

740

Pascual JM et al. K+ pore structure revealed by reporter cysteines at inner and outer surfaces.
Neuron, 1995 May , 14 (1055-63).

741

Christie MJ et al. Heteropolymeric potassium channels expressed in Xenopus oocytes from cloned subunits.
Neuron, 1990 Mar , 4 (405-11).

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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Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/188/ , accessed on 2024 Dec 21


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