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

Hydrogen sulfide inhibits Kir2 and Kir3 channels by decreasing sensitivity to the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2)

Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain, and other peripheral tissues. Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. The gasotransmitter carbon monoxide has been shown to regulate Kir channel activity by altering channel–PIP2 interactions. Here, we tested in two cellular models the effects and mechanism of action of another gasotransmitter, hydrogen sulfide (H2S), thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide as an exogenous H2S source and expression of cystathionine -lyase, a key enzyme that produces endogenous H2S in specific brain tissues, resulted in comparable current inhibition of several Kir2 and Kir3 channels. This effect resulted from changes in channel-gating kinetics rather than in conductance or cell-surface localization. The extent of H2S regulation depended on the strength of the channel–PIP2 interactions. H2S regulation was attenuated when channel–PIP2 interactions were strengthened and was increased when channel–PIP2 interactions were weakened by depleting PIP2 levels. These H2S effects required specific cytoplasmic cysteine residues in Kir3.2 channels. Mutation of these residues abolished H2S inhibition, and reintroduction of specific cysteine residues back into the background of the cytoplasmic cysteine-lacking mutant rescued H2S inhibition. Molecular dynamics simulation experiments provided mechanistic insights into how potential sulfhydration of specific cysteine residues could lead to changes in channel–PIP2 interactions and channel gating. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc

Sonic Cyberfeminisms: Introduction

Since the mid-2010s, there has been a surge of interest in the relations between sound, gender and technology. Debates taking place in contemporary arts, music, education and audio technology have pointed to the continued lack of women and non-binary people represented in these fields. Particularly in the technocentric fields relating to electronic-based musics and sound arts, a masculinist and heteronormative bias has compounded an often under-acknowledged hostility to feminist agendas of change or reform. Various initiatives, in the form of networks, conferences, educational programmes and online campaigns, have sought to redress this

Parenting gone wired: empowerment of new mothers on the Internet?

The extension of information and communication technologies is purported to provide great opportunities for women, with the potential for empowerment and feminist activism. This paper contributes to the debate about women and cyberspace through a focus on the role of the internet in the lives of a group of technologically proficient, socially advantaged white heterosexual new mothers. The internet played a central role in providing virtual social support and alternative information sources which increased these women’s real sense of empowerment in the transition to motherhood. Simultaneously, however, very traditional stereotypes of mothering and gender roles persisted. A paradox is evident whereby the internet was both liberating and constraining: it played an important social role for some women while at the same time it encouraged restrictive and unequal gender stereotypes in this particular community of practice. An examination of new virtual parenting spaces therefore has a contribution to make in understanding changing parenting practices in the new millennium. L'expansion des technologies de l'information et de la communication est censée pouvoir offrir de multiples possibilités aux femmes susceptibles de renforcer leur autonomie et le militantisme féministe. Cet article apporte un éclairage au débat sur les femmes et le cyberespace en examinant le rôle de l'Internet dans les vies d'un groupe composé de nouvelles mères de race blanche, hétérosexuelle, socialement plus avantagées et maîtrisant les nouvelles technologies. L'Internet a joué un rôle primordial dans le développement d'un milieu de soutien social virtuel et l'offre de sources alternatives d'informations qui ont permis d'accroître leur sentiment réel d'être autonome lors du passage au stade de la maternité. En parallèle, toutefois, les idées stéréotypées traditionnelles du maternage et des rôles sexospécifiques persistent. Un paradoxe émerge entre l'effet libérateur et contraignant de l'Internet: celui-ci a joué un rôle social important pour quelques femmes tandis qu'il a simultanément favorisé des stéréotypes liés au genre restreignants et inégaux au sein de cette communauté de pratique. L'étude des nouveaux espaces virtuels qui encadrent le métier de parent sert donc à mieux comprendre les pratiques des parents au nouveau millénaire. Se sugiere que el aumento de tecnologías de informática y comunicación les ofrece grandes oportunidades a las mujeres, con la posibilidad de empoderamiento y activismo feminista. Este papel contribuye al debate sobre mujeres y el ciberespacio por medio de un estudio del papel del internet en las vidas de un grupo de madres nuevas, blancas y heterosexuales, privilegiadas socialmente y muy competentes en el uso de nuevas tecnologías. El internet jugaba un papel importante al ofrecerles apoyo social virtual y fuentes alternativos de información, lo cual aumentaba el sentido de poder real que tenían estas mujeres en la transición hacia la maternidad. Sin embargo, simultaneamente, persistían estereotipos muy tradicionales de la maternidad y los papeles de los géneros. Existía una paradoja en que el internet les liberaba tanto como les limitaba. Jugaba un papel social importante para algunas mujeres pero, al mismo tiempo, fomentaba estereotipos de género limitantes y desiguales en esta comunidad de práctica. Como consecuencia, este estudio de nuevos espacios virtuales para madres tiene algo que contribuir a nuestro entendimiento de cambios en las prácticas de criar a los hijos en el nuevo milenio