title: Ion-channel modulators: more diversity than previously thought.
abstract: Ion-channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage dependence of activation/inactivation. Recent experiments performed on various ion channels show that allosteric modulation is an important mechanism for affecting channel function. For instance, in K(Ca)2 (formerly SK) channels, the prototypic "blocker" apamin prevents conduction by an allosteric mechanism, while TRPV1 channels are prevented from closing by a tarantula toxin, DkTx, through an interaction with residues located away from the selectivity filter. The recent evidence, therefore, suggests that in several ion channels, the region around the outer mouth of the pore is rich in binding sites and could be exploited therapeutically. These discoveries also suggest that the pharmacological vocabulary should be adapted to define these various actions.
authors: Laboratory of Medicinal Chemistry and CIRM, University of Liège, 1 Avenue de l'Hôpital, 4000 Liège, Belgium. sdilly@ulg.ac.be
authors: Sébastien
authors: S
authors: Dilly
authors: Cédric
authors: C
authors: Lamy
authors: Neil V
authors: NV
authors: Marrion
authors: Jean-François
authors: JF
authors: Liégeois
authors: Vincent
authors: V
authors: Seutin
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology*; D000495:Allosteric Site; D000595:Amino Acid Sequence; D001030:Apamin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D044822:Biodiversity; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport / Q000502:physiology*; D008564:Membrane Potentials; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013111:Spider Venoms / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D013111:Spider Venoms; D001030:Apamin; D011188:Potassium; D002118:Calcium