The recently discovered epithelial sodium channel (ENaC)/degenerin (DEG) gene family encodes sodium channels involved in various cell functions in metazoans. Subfamilies found in invertebrates or mammals are functionally distinct. The degenerins in Caenorhabditis elegans participate in mechanotransduction in neuronal cells, FaNaC in snails is a ligand-gated channel activated by neuropeptides, and the Drosophila subfamily is expressed in gonads and neurons. In mammals, ENaC mediates Na+ transport in epithelia and is essential for sodium homeostasis. The ASIC genes encode proton-gated cation channels in both the central and peripheral nervous system that could be involved in pain transduction. This review summarizes the physiological roles of the different channels belonging to this family, their biophysical and pharmacological characteristics, and the emerging knowledge of their molecular structure. Although functionally different, the ENaC/DEG family members share functional domains that are involved in the control of channel activity and in the formation of the pore. The functional heterogeneity among the members of the ENaC/DEG channel family provides a unique opportunity to address the molecular basis of basic channel functions such as activation by ligands, mechanotransduction, ionic selectivity, or block by pharmacological ligands.
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed co-receptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into use of IRs as genetically encoded chemical sensors.
Unlike plants, animals rely on rapid nervous systems to escape predation. A stationary fly that perceives danger takes less than 300 ms to take off, and this process requires complex whole- to ion fluxes in cell populations in wounded Arabidopsis plants. As summarised in Supplementary Fig. 1, we show that electrical signalling activates jasmonate biosynthesis in leaves distal to wounds and we identify genes involved in electrical signal propagation. Wound-induced surface potential changesTo investigate patterns of electrical activity and gene expression in 5 week-old rosettes, individual leaves were numbered from oldest to youngest. Electrodes placed on leaf 8 at the midrib/petiole junction (e2 electrode position) and on the petiole (position e3) did not detect changes in electrical activity and such changes were not elicited by walking S. littoralis larvae (Fig. 1b). When recordings were extended, they often showed periodicity ( Supplementary Fig. 3). We used three parameters to characterise these signals: latency (time from wounding to arrival at the amplitude midpoint), amplitude and duration (Fig. 1b). To gain more information on the spread of WASPs within a wounded leaf, four electrodes were placed on the leaf surface (Fig. 1a). After damage, WASPs were detected first at e1, then several seconds later at e2, and finally at e3. An electrode on the lamina also detected damage-elicited electrical activity and, in each case (Fig. 1c), the changes in amplitude were typically close to -70 mV (SupplementaryTable 1). The signals we measured had the same polarity as those produced after a chilling treatment known to cause plasma membrane depolarisation 24,25 . Therefore WASPs in leaf 8 were due to plasma membrane depolarisation ( Supplementary Fig. 4). The WASPs detected on WT plants were indistinguishable to those on wounded plants that lacked the ability to synthesize jasmonates ( Supplementary Fig. 5).This suggests that the mechanism that produces WASPs is upstream or independent of jasmonate synthesis. WASP territories and speedsSignals generated by wounding leaf tips first move towards the centre of the rosette and then disperse away from the apex into a restricted number of distal leaves to initiate distal JA accumulation and signalling 11 . In order to map the spatial distribution of WASPs in the rosette after wounding leaf 8 we placed electrodes in the e3 position of leaves 5 through 18. Leaves 5, 11, 13 and 16 showed responses similar to those in the wounded leaf (Fig. 1d, Supplementary Table 2). For example, after wounding leaf 8, a WASP with a duration of 78±20 s and a peak amplitude of -51 ± 9 mV was reached in leaf 13 after a latency of 66 ± 13 s (n=61 plants). Other leaves (7, 9, 10, 12, 14, 15,17 and 18) showed small positive surface potential changes. For example, leaf 9 showed a 20±5 mV change in surface potential with a latency of 54±12 s (n=46 plants). Most of these observations fit a developmental pattern: In adult-phase Arabidopsis rosettes, leaf 'n' shares direct vascular connections to leave...
The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (http://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14749. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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