Ion channels

File:1qrq1.png

Crystal structure of voltage-dependent potassium channel, 1qrq

Ion channels are membrane proteins that catalyze the passive transport of ions through the cell membrane. Most ion channels are specific to an ion, like the sodium channels, or the chloride channels. Some, like the TRP channels, let through various cations. Another property of ion channels is that they can be either driven by voltage or concentration gradients, or they can be gated (by voltage, ligands, touch and other sensory signal). Potassium channels (KCh) are subdivided to voltage-gated KCh and calcium-dependent KCh. The latter are subdivided into high- (BK, LKCa), intermediate- and small-conductance KCh (human SK1, rat SK2, SKCa). MthK is a calcium-dependent potassium channel from Methanobacterium thermoautrophicum. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane. Voltage-Dependent Calcium Channels (VDCC) allow Ca⁺⁺ to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. Finally, ion channels are the fastest of all membrane transporters, with 10⁶ to 10⁸ transported units per second versus 10² to 10⁴ molecules per second for porters/carriers, or 10⁰ to 10³ for ATP-driven pumps. The images at the left and at the right correspond to one representative ion channel structure, i.e. the crystal structure of voltage-dependent potassium channel from Rattus norvegicus (1qrq).

ClassificationClassification

TCDB, the most sophisticated classification of transport proteins to date, classify ion channels as a heterogenous subset of all α-type channels, whose singular property is to consist mainly of α-helices that span the membrane. They are distinct in this from the beta-barrel porins and the pore-forming toxins, as well as from non-ribosomally synthesized channels like gramicidin, polyglutamine or digitoxin. All these proteins are passive transport proteins.

Additional ResourcesAdditional Resources

For additional information, see: Membrane Channels & Pumps
For additional information, see: Hypertension & Congestive Heart Failure

Available 3D structuresAvailable 3D structures

Ion channels translate ionic fluxes across cell membrane into electrical impulses. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane. Voltage-Dependent Calcium Channels (VDCC) allow Ca to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. The human annexin V molecule serves as a calcium channel. There are also Voltage-Dependent Anion Channels (VDAC). Chloride ion channels (ClCh) are involved in maintaining pH, volume homeostasis and more. Ligand-Gated Ion Channels (LGIC) open or close when binding a ligand like a neurotransmitter. The Cyclic Nucleotide-Gated channel (CNGC) conduct cations upon binding of cAMP or cGMP. The Acid-Sensitive channels (ASC) conduct cations upon binding of acid. The glycerol facilitator (GlpF) is a protein channel which transports glycerol across the cell membrane of E. coli. Other ion channel proteins are the aquaporins, gramicidin, antiamoebin, trichotoxin, peptaibol and the glutamate receptor.

Potassium channelPotassium channel

See: Potassium Channels

Calcium channelCalcium channel

3bxx – rCav2.1 alpha 1A subunit+calmodulin
3bxl - rCav2.3 alpha 1E subunit+calmodulin
2f3y, 2f3z, 2be6 – hCav1.2 alpha 1C subunit+calmodulin
1t0h – rVDCC beta 2A subunit
1t0j – rVDCC beta 2A+alpha 1C
1vyt - rVDCC beta 3+alpha 1C
1vyu – rVDCC beta 3
1vyv - rVDCC beta 4
1t3l - raVDCC beta 2+alpha 1S – rabbit
1t3s - raVDCC beta 2
2d46 – hVDCC beta 4a – NMR
3dve, 3dvj, 3dvk, 3dvm, 3g43 - rCav2.2 alpha 1B subunit+hCalmodulin
3oxq - hCav2.1 alpha 1C subunit IQ domain+hCalmodulin
2vay - hCav1.1 alpha 1S subunit IQ domain+hCalmodulin
1hvd, 1hve, 1hvf, 1hvg – hAnnexin V (mutant)

Sodium channelSodium channel

1byy - rNaCh IIA inactivation fragment
2kav, 2kbi - hNaCh IIA C-terminal EF-hand domain - NMR

NH4+ channelNH4+ channel

2nmr, 2nop, 2now, 2npc, 2npd, 2npe, 2npj, 2npg, 2npk, 1u77, 1u7c, 1u7g, 1xqe, 1xqf – EcAmCh – Escherichia coli
2b2h, 2b2i, 2b2j, 2b2f – AmCh – Archaeglobus fulgidus
3b9w, 3b9y, 3bhs – AmCh – Nitrosomonas europaea

MscL and MscSMscL and MscS

3hzq – MscL – Staphylococcus aureus
2oar – MscL – Mycobacterium tuberculosis
2oau, 2vv5 - EcMscS

Chloride channelChloride channel

2ahe, 2d2z – hClCh protein 4
1rk4 - hClCh protein 1
3o3t, 3p8w, 3p90, 1k0o - hClCh protein 1 (mutant)
2per, 2r4v, 2r5g - hClCh protein 2

Anion ChannelAnion Channel

2jk4 – hVDAC

Ligand-gated ion channelLigand-gated ion channel

2vl0 – LGIC – Erwinia chrysanthemi
2xq3, 2xq4, 2xq5, 2xq6, 2xq7, 2xqa, 2xq8 – GvLGIC+inhibitor – Gloeobacter violaceus
3eam, 3ehz – GvLGIC
3igq – GvLGIC N-terminal
2xq9 – GvLGIC (mutant)+inhibitor
3lsv – GvLGIC (mutant)

Cyclic Nucleotide-Gated channelCyclic Nucleotide-Gated channel

3etq, 3ffq – mCNGC C-terminal
1q3e, 1q43, 1q5o - mCNGC 2 fragment + nucleotide
2q0a - mCNGC 2 C-terminal (mutant)
3bpz - mCNGC 2 ligand-binding domain
2zd9, 3beh - MlCNGC
2ptm - CNGC C-terminal - Strongylocentratus purpuratus

Acid sensitive ion channelAcid sensitive ion channel

3hgc, 3ij4, 2qts – ASC – chicken

ATP-Gated channel (AGC)ATP-Gated channel (AGC)

3h9v, 3i5d – AGC – Zebra fish

Proton channelProton channel

2kih, 2kwx – IVproton channel – Influenza virus
2rtf - IVproton channel + inhibitor - NMR
3c9j - IVproton channel transmembrane domain + inhibitor
2kj1, 2l0j - IVproton channel – NMR

Voltage-gated hydrogen channel (VGHC)Voltage-gated hydrogen channel (VGHC)

3a2a – hVGHC C-terminal - NMR

Nicotinic acetylcholine receptorNicotinic acetylcholine receptor

1oed, 2bg9 - AChR - Torpeco marmorata - EM
2k58 - AChR β2 subunit 1st transmembrane domain - NMR
2k59 - AChR β2 subunit - NMR

Tryptophan channelTryptophan channel

2rfa - mTrpCh ankyrin repeat domain
3e7k - rTrpCh tetramerization domain

Glycerol facilitatorGlycerol facilitator

1lda, 1ldi - EcGlpF
1fx8 - EcGlpF + glycerol
1ldf - EcGlpF (mutant)

WeblinksWeblinks

• The TCDB database
• TCDB: 1.A α-Type channels
• TCDB: Transport proteins with PDB structures