Ion channels: Difference between revisions

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[[Image:1qrq1.png|left|200px|thumb|Crystal structure of voltage-dependent potassium channel, [[1qrq]]]]
<StructureSection load='1qrq' size='340' side='right' caption='Voltage-dependent potassium channel β subunit core complex with NADPH, [[1qrq]]' scene=''>
{{STRUCTURE_1qrq|  PDB=1qrq  | SIZE=300| SCENE=Ion_channels/Cv/1 |right|CAPTION=voltage-dependent potassium channel, [[1qrq]] }}
== Function ==
[[Ion channels]] are membrane proteins that catalyze the passive transport of ions through the cell membrane. Ion channels are the fastest of all membrane transporters, with 10<sup>6</sup> to 10<sup>8</sup> transported units per second versus 10<sup>2</sup> to 10<sup>4</sup> molecules per second for porters/carriers, or 10<sup>0</sup> to 10<sup>3</sup> for ATP-driven pumps.


[[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 Channel|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).
== Ion channel types ==
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<sup>++</sup> 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 10<sup>6</sup> to 10<sup>8</sup> transported units per second versus 10<sup>2</sup> to 10<sup>4</sup> molecules per second for porters/carriers, or 10<sup>0</sup> to 10<sup>3</sup> 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]]).
Most ion channels are specific to an ion, like the '''sodium channels''', or the [[Potassium Channel]]<ref>PMID:19165895</ref>.<br />
*'''TRP channels''' let through various cations<ref>PMID:17579562</ref>.<br />
Another property of ion channels is that they can be either driven by voltage or by concentration gradients, or they can be gated (by voltage, ligands, touch and other sensory signal).<br />
*'''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). See: [[Potassium Channel|Potassium channels]].<br />
*'''MthK''' is a calcium-dependent potassium channel from ''Methanobacterium thermoautrophicum''<ref>PMID:16735753</ref>.<br />
*'''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<ref>PMID:12046893</ref>.<br />
See:<br />
[[Mechanosensitive channels: opening and closing]].<br />
*'''Voltage-Dependent Calcium Channels''' (VDCC) allow calcium ions 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<ref>PMID:16096350</ref>. <br />
See:<br />
[[Voltage-gated calcium channels]].<br />
[[Voltage-gated calcium channel Cav1.1 complex]].<br />


{{TOC limit|limit=2}}
*'''Voltage-gated sodium (Nav) channels''' - see:
*[[Bupivacaine]]
*[[Carbamazepine]]
 
There are also '''Voltage-Dependent Anion Channels''' (VDAC)<ref>PMID:16787253</ref>.<br />
*'''Chloride ion channels''' (ClCh) are involved in maintaining pH, volume homeostasis and more.  The anti-parasitic drug [[Ivermectin]] binds to glutamate-gated chloride channels.<br />
See:<br />
[[Chloride Ion Channel]]<br />
[[User:Laura Fountain/Chloride Ion Channel]]<br />
[[Chloride Intracellular Channel Protein 2]]<br />
*'''Calcium-activated chloride channel''' or '''anoctamin''' or '''scramblase''' or '''TMEM16''' are important in cell volume regulation and malignancy<ref>PMID:21607626</ref>.<br />
*'''Bestrophin''' is another type of '''Calcium-activated chloride channel'''<ref>PMID:22183384</ref><br />
*'''Ligand-Gated Ion Channels''' (LGIC) open or close when binding a ligand like a neurotransmitter<ref>PMID:15288758</ref>.<br />
See [[Journal:Acta_Cryst_D:S205979832000772X|Structural evidence for mono- and di-carboxylates binding at pharmacologically relevant extracellular sites of a pentameric ligand gated ion channel]] <ref>doi 10.1107/S205979832000772X</ref>
 
*'''Cyclic Nucleotide-Gated channels''' (CNGC) conduct cations upon binding of cAMP or cGMP<ref>PMID:12087135</ref>.<br />
*'''Acid-Sensitive channels''' (ASC) conduct cations upon binding of acid<ref>PMID:19655111</ref>.<br />
*'''Transient receptor potential cation channel''' (TRP)  superfamily consists of 6 subfamilies: canonical, melastatin-related, ankyrin, mucolipin, mucolipidosis, polycystic and vanilloid (TRPV) which is heat-sensitive <ref>PMID:15288758</ref>.  For details see [[Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1)]].<br />
*'''Glycerol facilitator''' (GlpF) is a protein channel which transports glycerol across the cell membrane of ''E. coli''<ref>PMID:12948772</ref>.<br />
Other ion channel proteins are the aquaporins, annexin V, gramicidin, antiamoebin, trichotoxin, peptaibol and the glutamate receptor.  Specific details in:<br />
*[[Proton Channels]], <br />
*[[Membrane Channels & Pumps]],<br />
*[[M2 Proton Channel]],  <br />
*[[M2 Proton Channel Inhibitor Pharmacokinetics]], <br />
*[[User:Michael Strong/H1N1/MP]] give details on proton channels,<br />
*[[User:Michael Strong/H1N1/MP1/MSA]],<br />
*[[User:Michael Strong/H1N1/MP2/MSA]] for multiple sequence alignment<br />   
*[[Ryanodine receptor]].<br />
*[[Hypertension & Congestive Heart Failure]].
*[[5-hydroxytryptamine receptor#Structural highlights/Specific Function of 5-HT3|5-HT3 receptor]]
== Classification ==
== Classification ==
TCDB, the most sophisticated classification of transport proteins to date, classify ion channels as a heterogenous subset of all '''&alpha;-type channels''', whose singular property is to consist mainly of [[alpha helix|&alpha;-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.
TCDB, the most sophisticated classification of transport proteins to date, classify ion channels as a heterogenous subset of all '''&alpha;-type channels''', whose singular property is to consist mainly of [[alpha helix|&alpha;-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.
 
== Disease ==
Mutations in sodium channel are involved in arrhythmia<ref>PMID:19377496</ref>, epilepsy<ref>PMID:16075041</ref>, Brugada syndrome and cardiac conduction disease<ref>PMID:18464934</ref>.  Many diseases are related to voltage-gated sodium, potassium, chloride, acetylcholine and glycine ion channels<ref>PMID:11310970</ref>.  Mutations in several members of the calcium-activated chloride channels or anoctamin are liked to several diseases: ano-1 to cancer, ano-5 to muscular dystrophy, ano-10 to ataxia and ano-6 to Scott syndrome<ref>PMID:21642943</ref><br />  Mutations in bestrophin are associated with macular dystrophy<ref>PMID:24328569</ref>.<br />[[Amiodarone]] and [[Amlodipine]] are voltage-gated calcium channel blockers used in treatment of cardiac dysrhythmias.


==Additional Resources==
==Additional Resources==
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<br />
<br />


== Available 3D structures ==
== 3D structures of ion channels ==
Membrane transport proteins are notoriously difficult to crystallize while in a working state. So, it's no == === Potassium channel ===
[[Ion channels 3D structures]]
 
See: [[Potassium_Channel#Additional_Structures_of_Potassium_Channels|Potassium Channels]]
=== BK channel ===
 
[[3mt5]] – hBK cytoplasmic domain<br />
[[1jo6]] – BK beta 2 N- terminal KCNMB2 encoded LKCa  - NMR
 
 
=== MthK ===
 
[[1kxd]] – MthK RCK domain+Cd - ''Methanobacterium thermoautrophicum''<br />
[[2ogu]], [[2fy8]], [[2aej]], [[2aem]], [[1lnq]] - MthK RCK domain<br />
[[2aef]] - MthK RCK domain+Ca
 
 
=== Calcium channel ===
 
[[3bxx]] – rCav2.1 alpha 1A subunit+calmodulin<br />
[[3bxl]] - rCav2.3 alpha 1E subunit+calmodulin<br />
[[2f3y]], [[2f3z]], [[2be6]] – hCav1.2 alpha 1C subunit+calmodulin<br />
[[1t0h]] – rVDCC beta 2A subunit <br />
[[1t0j]] – rVDCC beta 2A+alpha 1C <br />
[[1vyt]] - rVDCC beta 3+alpha 1C <br />
[[1vyu]] – rVDCC beta 3<br />
[[1vyv]] - rVDCC beta 4<br />
[[1t3l]] - raVDCC beta 2+alpha 1S – rabbit<br />
[[1t3s]] - raVDCC beta 2<br />
[[2d46]] – hVDCC beta 4a – NMR<br />
[[3dve]], [[3dvj]], [[3dvk]], [[3dvm]], [[3g43]] - rCav2.2 alpha 1B subunit+hCalmodulin<br />
[[3oxq]] - hCav2.1 alpha 1C subunit IQ domain+hCalmodulin<br />
[[1hvd]], [[1hve]], [[1hvf]], [[1hvg]] – hAnnexin V (mutant)
 
 
=== NH4+ channel ===
 
[[2nmr]], [[2nop]], [[2now]], [[2npc]], [[2npd]], [[2npe]], [[2npj]], [[2npg]], [[2npk]], [[1u77]], [[1u7c]], [[1u7g]], [[1xqe]], [[1xqf]] – EcAmCh – ''Escherichia coli''<br />
[[2b2h]], [[2b2i]], [[2b2j]] – AmCh – ''Archaeglobus fulgidus''<br />
[[3b9w]], [[3b9y]] – AmCh – ''Nitrosomonas  europaea''
 
=== MscL and MscS ===
 
[[3hzq]] – MscL – ''Staphylococcus aureus''<br />
[[2oar]] – MscL – ''Mycobacterium tuberculosis''<br />
[[2oau]], [[2vv5]] - EcMscS


 
</StructureSection>
=== Chloride channel ===
 
[[2ahe]], [[2d2z]] – hClCh protein 4<br />
[[1rk4]] - hClCh protein 1<br />
[[3o3t]], [[3p8w]], [[3p90]], [[1k0o]] - hClCh protein 1 (mutant)
 
 
=== Anion Channel ===
 
[[2jk4]] – hVDAC
 
 
=== Ligand-gated ion channel ===
 
[[2vl0]] – LGIC – ''Erwinia chrysanthemi''<br />
[[2xq3]], [[2xq4]], [[2xq5]], [[2xq6]], [[2xq7]], [[2xqa]], [[2xq8]] – GvLGIC+inhibitor – ''Gloeobacter violaceus''<br />
[[3eam]], [[3ehz]] – GvLGIC<br />
[[3igq]] – GvLGIC N-terminal<br />
[[2xq9]] – GvLGIC (mutant)+inhibitor<br />
[[3lsv]] – GvLGIC (mutant)
 
 
=== Cyclic Nucleotide-Gated channel ===
 
[[3etq]], [[3ffq]] – mCNGC C-terminal<br />
[[2zd9]], [[3beh]] - MlCNGC
 
 
=== Acid sensitive ion channel ===
 
[[3hgc]], [[3ij4]] – ASC – chicken
 
 
=== ATP-Gated channel (AGC) ===
 
[[3h9v]], [[3i5d]] – AGC – Zebra fish
 
 
=== Proton channel ===
 
[[2kih]], [[2kwx]] – IVproton channel – Influenza virus<br />
[[2kj1]], [[2l0j]] - IVproton channel – NMR
 
 
== Voltage-gated hydrogen channel (VGHC) ==
[[3a2a]] – hVGHC C-terminal - NMR


== Weblinks ==
== Weblinks ==
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*[http://www.tcdb.org/tcdb/subclass2.php?tc=1.A TCDB: 1.A α-Type channels]
*[http://www.tcdb.org/tcdb/subclass2.php?tc=1.A TCDB: 1.A α-Type channels]
*[http://www.tcdb.org/pdb_structure.php TCDB: Transport proteins with PDB structures]
*[http://www.tcdb.org/pdb_structure.php TCDB: Transport proteins with PDB structures]
== References ==
<references/>


[[Category:Topic Page]]
[[Category:Topic Page]]

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Ralf Stephan, Ilan Samish, Eric Martz, Wayne Decatur, Alexander Berchansky, Michal Harel, David Canner, Jaime Prilusky, Shelly Livne