Nerve terminal GABAA receptors activate Ca2+/calmodulin-dependent signaling to inhibit voltage-gated Ca2+ influx and glutamate release

-Aminobutyric acid type A (GABAA) receptors, a family of Cl-permeable ion channels, mediate fast synaptic inhibition as postsynaptically enriched receptors for -aminobutyric acid at GABAergic synapses. Here we describe an alternative type of inhibition mediated byGABAA receptors present on neocortical glutamatergic nerve terminals and examine the underlying signaling mechanism(s). By monitoring the activity of the presynaptic CaM kinase II/synapsin I signaling pathway in isolated nerve terminals, we demonstrate that GABAA receptor activation correlated with an increase in basal intraterminal [Ca2]i. Interestingly, this activation of GABAA receptors resulted in a reduction of subsequent depolarization-evoked Ca2 influx, which thereby led to an inhibition of glutamate release. To investigate how the observed GABAA receptor-mediated modulation operates, we determined the sensitivity of this process to the Na-K-2Cl cotransporter 1 antagonist bumetanide, as well as substitution of Ca2 with Ba2, or Ca2/calmodulin inhibition by W7. All of these treatments abolished the modulation by GABAA receptors. Application of selective antagonists of voltage-gated Ca2 channels (VGCCs) revealed that the GABAA receptor-mediated modulation of glutamate release required the specific activity of L- and R-type VGCCs. Crucially, the inhibition of release by these receptors was abolished in terminals isolated from R-type VGCC knock-out mice. Together, our results indicate that a functional coupling between nerve terminal GABAA receptors and L- or R-type VGCCs is mediated by Ca2/calmodulin-dependent signaling. This mechanism provides a GABA-mediated control of glutamatergic synaptic activity by a direct inhibition of glutamate release.

The Dark Monarch: magic and modernity in British art

This major curated exhibition, publication and events builds on Rowlands’ curatorial research. Working in collaboration with co-curators Martin Clark, Artistic Director, Tate St Ives and Michael Bracewell, cultural historian, the exhibition sought to explore new narratives within British art. The innovative curatorial methodology developed from a fiction found in the infamous novel, The Dark Monarch by Sven Berlin, Gallery Press 1962. The research sought specific archival and collection work that allowed thematic strands to emerge that represented influences across generations. The exhibition features two-hundred artworks, from the Tate Collection, archives and other significant British public and private collections. It examines the development of early Modernism, in the UK, as well as the reappearance of esoteric and arcane references in a significant strand of contemporary art practice. Historical works from Samuel Palmer, Graham Sutherland, Henry Moore and Paul Nash are shown alongside contemporary artists including Derek Jarman, Cerith Wyn Evans, Eva Rothschild, Linder and John Russell. The exhibition includes a key work by Damien Hirst ¬ the first time he has been shown at Tate St Ives and a number of contemporary commissions. The Dark Monarch publication extended the discourse of the research critically examining the tension between progressive modernity and romantic knowledge, the book focuses on the way that artworks are encoded with various histories - geological, mythical and magical. Essays examine magic as a counterpoint to modernity’s transparency and rational progress, but also draw out the links modernity has with notions such as fetishism, mana, totem, and the taboo. Often viewed as counter to Modernism, this collection of essays suggest that these products of illusion and delusion in fact belong to modernity. Drawing together 15 different writers commissioned to explore magic as a counterpoint of liberal understanding of modernity, drawing out links that modernity has with notions of fetish, taboo and occult philosophy. Including essays by Marina Warner, Ilsa Colsell, Philip Hoare, Chris Stephens, Jennifer Higgie and Morrissey.

Ethel Carnie Holdsworth (1886-1962), ex-mill girl novelist

This short article explores the life and work of Ethel Carnie Holdsworth, the first working-class woman in Britain to publish full-length novels. It assesses her politics and her literacy legacy and is part of the Women's History Network's series, 'Reclaiming Women's Histories'.

On the environmental valuation of catastrophe: revisiting mining disasters in the United Kingdom, 1851-1962

In the context of environmental valuation of natural disasters, an important component of the evaluation procedure lies in determining the periodicity of events. This paper explores alternative methodologies for determining such periodicity, illustrating the advantages and the disadvantages of the separate methods and their comparative predictions. The procedures employ Bayesian inference and explore recent advances in computational aspects of mixtures methodology. The procedures are applied to the classic data set of Maguire et al (Biometrika, 1952) which was subsequently updated by Jarrett (Biometrika, 1979) and which comprise the seminal investigations examining the periodicity of mining disasters within the United Kingdom, 1851-1962.