- Advanced search
Ion channels are pore-forming proteins that allow the flow of ions across membranes, either plasma membranes, or the membranes of intracellular organelles . Many ion channels (such as most Na, K, Ca and some Cl channels) are gated by voltage but others (such as certain K and Cl channels, TRP channels, ryanodine receptors and IP3 receptors) are relatively voltage-insensitive and are gated by second messengers and other intracellular and/or extracellular mediators. As such, there is some blurring of the boundaries between "ion channels" and "ligand-gated channels" which are compiled separately in the Guide. Resolution of ion channel structures, beginning with K channels  then Cl channels  and most recently Na channels  has greatly improved understanding of the structural basis behind ion channel function. Many ion channels (e.g., K, Na, Ca, HCN and TRP channels) share several structural similarities. These channels are thought to have evolved from a common ancestor and have been classfied together as the "voltage-gated-like (VGL) ion channel chanome" (see ). Other ion channels, however, such as Cl channels, aquaporins and connexins, have completely different structural properties to the VGL channels, having evolved quite separately.
Currently, ion channels (including ligand-gated ion channels) represent the second largest target for existing drugs after G protein-coupled receptors . However, the advent of novel, faster screening techniques for compounds acting on ion channels  suggests that these proteins represent promising targets for the development of additional, novel therapeutic agents for the near future.
1. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 280 (5360): 69-77. [PMID:9525859]
2. Dunlop J, Bowlby M, Peri R, Vasilyev D, Arias R. (2008) High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nat Rev Drug Discov, 7 (4): 358-68. [PMID:18356919]
3. Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R. (2002) X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nature, 415 (6869): 287-94. [PMID:11796999]
4. Hille B. (1986) Ionic channels: molecular pores of excitable membranes. Harvey Lect., 82: 47-69. [PMID:2452140]
5. Overington JP, Al-Lazikani B, Hopkins AL. (2006) How many drug targets are there?. Nat Rev Drug Discov, 5 (12): 993-6. [PMID:17139284]
6. Payandeh J, Scheuer T, Zheng N, Catterall WA. (2011) The crystal structure of a voltage-gated sodium channel. Nature, 475 (7356): 353-8. [PMID:21743477]
7. Yu FH, Yarov-Yarovoy V, Gutman GA, Catterall WA. (2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol. Rev., 57 (4): 387-95. [PMID:16382097]
Database page citation:
Ion channels. Accessed on 25/02/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=689.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Buneman OP, Catterall WA, Cidlowski JA, Davenport AP, Fabbro D, Fan G, McGrath JC, Spedding M, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Overview. Br J Pharmacol. 172: 5729-5743.