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Voltage-gated potassium channel



Potassium channel KvAP, structure in a membrane-like environment. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue dots.
Ion channel (eukariotic)
Identifiers
Symbol Ion_trans
Pfam PF00520
InterPro IPR005821
SCOP 1bl8
TCDB 1.A.1
OPM family 8
OPM protein 2a79
Available PDB structures:

1qg9A:157-176 2a79B:225-409 1ho7A:378-397 1ho2A:378-397 1ujlA:570-611

Potassium channel KcsA. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue dots.
Ion channel (bacterial)
Identifiers
Symbol Ion_trans_2
Pfam PF07885
InterPro IPR013099
SCOP 1bl8
OPM protein 1r3j
Available PDB structures:

1lnqE:25-100 2a0lB:169-250 1orqC:169-250 1k4cC:34-116 1r3iC:34-116 2bocC:34-116 1j95C:34-116 1r3lC:34-116 1jvmB:34-116 1bl8C:34-116 2a9hD:34-116 1k4dC:34-116 1r3jC:34-116 1r3kC:34-116 2bobC:34-116 1p7bB:77-151

Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. They play a crucial role during action potentials in returning the depolarized cell to a resting state.

Additional recommended knowledge

Contents

Classification

Alpha subunits

Alpha subunits form the actual conductance pore. Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels have been grouped into 12 classes labeled Kv1-12.[1] The following is a list of the 40 known human voltage-gated potassium channel alpha subunits grouped first according to function and then subgrouped according to the Kv sequence homology classification scheme:

Delayed rectifier

non-inactivating

  • Kvα1.x - Shaker-related: Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.4 (KCNA4), Kv1.5 (KCNA5), Kv1.6 (KCNA6), Kv1.7 (KCNA7), Kv1.8 (KCNA10)
  • Kvα2.x - Shab-related: Kv2.1 (KCNB1), Kv2.2 (KCNB2)
  • Kvα3.x - Shaw-related: Kv3.1 (KCNC1), Kv3.2 (KCNC2)
  • Kvα7.x: Kv7.1 (KCNQ1) - KvLQT1, Kv7.2 (KCNQ2), Kv7.3 (KCNQ3), Kv7.4 (KCNQ4), Kv7.5 (KCNQ5)
  • Kvα10.x: Kv10.1 (KCNH1)

A-type potassium channel

rapidly inactivating

  • Kvα3.x - Shaw-related: Kv3.3 (KCNC3), Kv3.4 (KCNC4)
  • Kvα4.x - Shal-related: Kv4.1 (KCND1), Kv4.2 (KCND2), Kv4.3 (KCND3)

Outward-rectifying

  • Kvα10.x: Kv10.2 (KCNH2)

Inward-rectifying

  • Kvα11.x - ether-a-go-go potassium channels: Kv11.1 (KCNH2) - hERG, Kv11.2 (KCNH6), Kv11.3 (KCNH7)

Slowly activating

  • Kvα12.x: Kv12.1 (KCNH8), Kv12.2 (KCNH3), Kv12.3 (KCNH4)

Modifier/silencer

Unable to form functional channels as homotetramers but instead heterotetramerize with Kvα2 family members to form conductive channels.

  • Kvα5.x: Kv5.1 (KCNF1)
  • Kvα6.x: Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4)
  • Kvα8.x: Kv8.1 (KCNV1), Kv8.2 (KCNV2)
  • Kvα9.x: Kv9.1 (KCNS1), Kv9.2 (KCNS2), Kv9.3 (KCNS3)

Beta subunits

Beta subunits are auxiliary proteins which associate with alpha subunits in a α4β4 stoichiometry.[2] These subunits do not conduct current on their own but rather modulate the activity of Kv channels.[3]

  • Kvβ1 (KCNAB1)
  • Kvβ2 (KCNAB2)
  • Kvβ3 (KCNAB3)
  • minK[4] (KCNE1)
  • MiRP1[5] (KCNE2)
  • MiRP2 (KCNE3)
  • MiRP3 (KCNE4)
  • KCNE1-like (KCNE1L)
  • KCNIP1 (KCNIP1)
  • KCNIP2 (KCNIP2)
  • KCNIP3 (KCNIP3)
  • KCNIP4 (KCNIP4)

Proteins minK and MiRP1 are putative hERG beta subunits.[6]

Animal research

The voltage-gated K+ channels that provide the outward currents of action potentials have similarities to bacterial K+ channels.

These channels have been studied by X-ray diffraction, allowing determination of structural features at atomic resolution.

The function of these channels is explored by electrophysiological studies.

Genetic approaches include screening for behavioral changes in animals with mutations in K+ channel genes. Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene sequences were well known.

Study of the altered properties of voltage-gated K+ channel proteins produced by mutated genes has helped reveal the functional roles of K+ channel protein domains and even individual amino acids within their structures.

Structure

Voltage-gated K+ channels of vertebrates typically are tetramers of four identical subunits arranged as a ring, each contributing to the wall of the trans-membrane K+ pore. Each subunit is comprised of six membrane spanning hydrophobic α-helical sequences. A high resolution crystallographic structure of the rat Kvα1.2/β2 channel has recently been solved (Protein Databank Accession Number 2A79).[7], and then refined in a lipid membrane-like environment (PDB 2r9r).

Selectivity

Voltage-gated K+ channels are selective for K+ over other cations such as Na+. There is a selectivity filter at the narrowest part of the transmembrane pore.

Channel mutation studies revealed the parts of the subunits that are essential for ion selectivity. They include the amino acid sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K+ channels. As K+ passes through the pore, interactions between potassium ions and water molecules are prevented and the K+ interacts with specific atomic components of the Thr-Val-Gly-X-Gly sequences from the four channel subunits[1].

Open and closed conformations

Attempts continue to relate the structure of the mammalian voltage-gated K+ channel to its ability to respond to the voltage that exists across the membrane.[8] Specific domains of the channel subunits have been identified that are important for voltage-sensing and converting between the open conformation of the channel and closed conformations. There are at least two closed conformations; in one, the channel can open if the membrane potential becomes positive inside. Voltage-gated K+ channels inactivate after opening, entering a distinctive, second closed conformation. In the inactivated conformation, the channel cannot open, even if the transmembrane voltage is favorable. A domain at one end of the K+ channel protein mediates inactivation. This end of the protein can transiently plug the inner opening of the pore, preventing ion movement through the channel.

See also

References

  1. ^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.". Pharmacol Rev 57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104.
  2. ^ Pongs O, Leicher T, Berger M, Roeper J, Bahring R, Wray D, Giese KP, Silva AJ, Storm JF (1999). "Functional and molecular aspects of voltage-gated K+ channel beta subunits". Ann N Y Acad Sci 868 (Apr 30): 344-55. PMID 10414304.
  3. ^ Li Y, Um SY, McDonald TV (2006). "Voltage-gated potassium channels: regulation by accessory subunits". Neuroscientist 12 (3): 199-210. PMID 16684966.
  4. ^ Zhang M, Jiang M, Tseng GN (2001). "minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?". Circ Res 88 (10): 1012-9. doi:10.1161/hh1001.090839. PMID 11375270.
  5. ^ McCrossan ZA, Abbott GW (2004). "The MinK-related peptides". Neuropharmacology 47 (6): 787-821. doi:10.1016/j.neuropharm.2004.06.018. PMID 15527815.
  6. ^ Anantharam A, Abbott GW (2005). "Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1". Novartis Found Symp 266 (42): 112-7, 155-8. doi:10.1002/047002142X.fmatter. PMID 16050264.
  7. ^ Long SB, Campbell EB, Mackinnon R (2005). "Crystal structure of a mammalian voltage-dependent Shaker family K+ channel". Science 309 (5736): 897-903. doi:10.1126/science.1116269. PMID 16002581.
  8. ^ Lee S, Lee A, Chen J, MacKinnon R (2005). "Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.". Proc Natl Acad Sci U S A 102 (43): 15441-6. PMID 16223877.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Voltage-gated_potassium_channel". A list of authors is available in Wikipedia.
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