The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 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.16178. 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-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

DIFFERENTIAL CEREBELLAR GABA(A) RECEPTOR EXPRESSION IN MICE WITH MUTATIONS IN CAV2.1 (P/Q-TYPE) CALCIUM CHANNELS

Functional Genomics of Muscle, Nerve and Brain Disorder

Activation of corticotropin-releasing factor receptor 1 selectively inhibits CaV3.2 T-type calcium channels

10.1124/mol.107.043612Molecular Pharmacology7361596-160

Histone methylation-mediated microRNA-32-5p down-regulation in sensory neurons regulates pain behaviors via targeting Cav3.2 channels.

SignificanceIn this study, we identify microRNA-32-5p (miR-32-5p) as a key functional noncoding RNA in trigeminal-mediated neuropathic pain. We report that injury-induced histone methylation attenuates the binding of glucocorticoid receptor to the promoter region of the miR-32-5p gene and decreases the expression of miR-32-5p, in turn promoting the development of neuropathic pain through regulation of Cav3.2 channels. miRNA-mediated gene regulation has been proposed as a therapeutic approach in neuropathic pain. Our findings identify miR-32-5p replenishment as a therapeutic strategy for treating chronic neuropathic pain

In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

Functional Genomics of Muscle, Nerve and Brain Disorder

Brainstem spreading depolarization and cortical dynamics during fatal seizures in Cacna1a S218L mice

Functional Genomics of Muscle, Nerve and Brain Disorder

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage

A novel, conserved gene of the rat that is developmentally regulated in the testis.

From a rat testis library three overlapping cDNA clones were isolated that represent a novel single-copy gene, designated Tegt. Two transcripts of 2.8 and 1.0 kb were found in each organ tested. The shorter transcript was highly abundant in adult testis. A similar expression pattern was found in the mouse. Analysis of rat RNA from different stages of spermatogenesis indicated that accumulation of the short transcript occurred mainly postmeiotically. The rat Tegt gene maps to Chromosome (Chr) 7, and its mouse homolog to Chr 15.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe