Ion channels

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Contents

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 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.

Ion channel types

Most ion channels are specific to an ion, like the sodium channels, or the Potassium Channel[1].

  • TRP channels let through various cations[2].

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).

  • 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 channels.
  • MthK is a calcium-dependent potassium channel from Methanobacterium thermoautrophicum[3].
  • 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[4].

See:
Mechanosensitive channels: opening and closing.

  • 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[5].

See:
Voltage-gated calcium channels.
Voltage-gated calcium channel Cav1.1 complex.

There are also Voltage-Dependent Anion Channels (VDAC)[6].

  • Chloride ion channels (ClCh) are involved in maintaining pH, volume homeostasis and more. The anti-parasitic drug Ivermectin binds to glutamate-gated chloride channels.

See:
Chloride Ion Channel
User:Laura Fountain/Chloride Ion Channel
Chloride Intracellular Channel Protein 2

  • Calcium-activated chloride channel or anoctamin or scramblase or TMEM16 are important in cell volume regulation and malignancy[7].
  • Bestrophin is another type of Calcium-activated chloride channel[8]
  • Ligand-Gated Ion Channels (LGIC) open or close when binding a ligand like a neurotransmitter[9].

See Structural evidence for mono- and di-carboxylates binding at pharmacologically relevant extracellular sites of a pentameric ligand gated ion channel [10]

  • Cyclic Nucleotide-Gated channels (CNGC) conduct cations upon binding of cAMP or cGMP[11].
  • Acid-Sensitive channels (ASC) conduct cations upon binding of acid[12].
  • 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 [13]. For details see Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1).
  • Glycerol facilitator (GlpF) is a protein channel which transports glycerol across the cell membrane of E. coli[14].

Other ion channel proteins are the aquaporins, annexin V, gramicidin, antiamoebin, trichotoxin, peptaibol and the glutamate receptor. Specific details in:

Classification

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.

Disease

Mutations in sodium channel are involved in arrhythmia[15], epilepsy[16], Brugada syndrome and cardiac conduction disease[17]. Many diseases are related to voltage-gated sodium, potassium, chloride, acetylcholine and glycine ion channels[18]. 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[19]
Mutations in bestrophin are associated with macular dystrophy[20].
Amiodarone and Amlodipine are voltage-gated calcium channel blockers used in treatment of cardiac dysrhythmias.

Additional Resources

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

3D structures of ion channels

Ion channels 3D structures


Voltage-dependent potassium channel β subunit core complex with NADPH, 1qrq

Drag the structure with the mouse to rotate

Weblinks

References

  1. ↑ Szewczyk A, Jarmuszkiewicz W, Kunz WS. Mitochondrial potassium channels. IUBMB Life. 2009 Feb;61(2):134-43. doi: 10.1002/iub.155. PMID:19165895 doi:http://dx.doi.org/10.1002/iub.155
  2. ↑ Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem. 2007;76:387-417. PMID:17579562 doi:http://dx.doi.org/10.1146/annurev.biochem.75.103004.142819
  3. ↑ Zadek B, Nimigean CM. Calcium-dependent gating of MthK, a prokaryotic potassium channel. J Gen Physiol. 2006 Jun;127(6):673-85. PMID:16735753 doi:http://dx.doi.org/10.1085/jgp.200609534
  4. ↑ Kloda A, Martinac B. Mechanosensitive channels of bacteria and archaea share a common ancestral origin. Eur Biophys J. 2002 Mar;31(1):14-25. PMID:12046893
  5. ↑ Lacinova L. Voltage-dependent calcium channels. Gen Physiol Biophys. 2005 Jun;24 Suppl 1:1-78. PMID:16096350
  6. ↑ Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu SS. The voltage-dependent anion channel (VDAC): function in intracellular signalling, cell life and cell death. Curr Pharm Des. 2006;12(18):2249-70. PMID:16787253
  7. ↑ Kunzelmann K, Tian Y, Martins JR, Faria D, Kongsuphol P, Ousingsawat J, Thevenod F, Roussa E, Rock J, Schreiber R. Anoctamins. Pflugers Arch. 2011 Aug;462(2):195-208. doi: 10.1007/s00424-011-0975-9. Epub 2011, May 21. PMID:21607626 doi:http://dx.doi.org/10.1007/s00424-011-0975-9
  8. ↑ Strauss O, Neussert R, Muller C, Milenkovic VM. A potential cytosolic function of bestrophin-1. Adv Exp Med Biol. 2012;723:603-10. doi: 10.1007/978-1-4614-0631-0_77. PMID:22183384 doi:http://dx.doi.org/10.1007/978-1-4614-0631-0_77
  9. ↑ Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Prog Biophys Mol Biol. 2004 Oct;86(2):161-204. PMID:15288758 doi:http://dx.doi.org/10.1016/j.pbiomolbio.2003.09.002
  10. ↑ Fourati Z, Sauguet L, Delarue M. Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel. Acta Crystallogr D Struct Biol. 2020 Jul 1;76(Pt 7):668-675. PMID:32627739 doi:10.1107/S205979832000772X
  11. ↑ Kaupp UB, Seifert R. Cyclic nucleotide-gated ion channels. Physiol Rev. 2002 Jul;82(3):769-824. PMID:12087135 doi:http://dx.doi.org/10.1152/physrev.00008.2002
  12. ↑ Holzer P. Acid-sensitive ion channels and receptors. Handb Exp Pharmacol. 2009;(194):283-332. doi: 10.1007/978-3-540-79090-7_9. PMID:19655111 doi:http://dx.doi.org/10.1007/978-3-540-79090-7_9
  13. ↑ Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Prog Biophys Mol Biol. 2004 Oct;86(2):161-204. PMID:15288758 doi:http://dx.doi.org/10.1016/j.pbiomolbio.2003.09.002
  14. ↑ Stroud RM, Miercke LJ, O'Connell J, Khademi S, Lee JK, Remis J, Harries W, Robles Y, Akhavan D. Glycerol facilitator GlpF and the associated aquaporin family of channels. Curr Opin Struct Biol. 2003 Aug;13(4):424-31. PMID:12948772
  15. ↑ Ruan Y, Liu N, Priori SG. Sodium channel mutations and arrhythmias. Nat Rev Cardiol. 2009 May;6(5):337-48. doi: 10.1038/nrcardio.2009.44. PMID:19377496 doi:http://dx.doi.org/10.1038/nrcardio.2009.44
  16. ↑ Meisler MH, Kearney JA. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest. 2005 Aug;115(8):2010-7. PMID:16075041 doi:http://dx.doi.org/10.1172/JCI25466
  17. ↑ Watanabe H, Koopmann TT, Le Scouarnec S, Yang T, Ingram CR, Schott JJ, Demolombe S, Probst V, Anselme F, Escande D, Wiesfeld AC, Pfeufer A, Kaab S, Wichmann HE, Hasdemir C, Aizawa Y, Wilde AA, Roden DM, Bezzina CR. Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. 2008 Jun;118(6):2260-8. doi: 10.1172/JCI33891. PMID:18464934 doi:http://dx.doi.org/10.1172/JCI33891
  18. ↑ Dworakowska B, Dolowy K. Ion channels-related diseases. Acta Biochim Pol. 2000;47(3):685-703. PMID:11310970
  19. ↑ Duran C, Hartzell HC. Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels? Acta Pharmacol Sin. 2011 Jun;32(6):685-92. doi: 10.1038/aps.2011.48. PMID:21642943 doi:http://dx.doi.org/10.1038/aps.2011.48
  20. ↑ Pasquay C, Wang LF, Lorenz B, Preising MN. Bestrophin 1--Phenotypes and Functional Aspects in Bestrophinopathies. Ophthalmic Genet. 2015;36(3):193-212. doi: 10.3109/13816810.2013.863945. PMID:24328569 doi:http://dx.doi.org/10.3109/13816810.2013.863945
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