Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

GABA Maintains the Proliferation of Progenitors in the Developing Chick Ciliary Marginal Zone and Non-Pigmented Ciliary Epithelium

GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABAA receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABAA receptor system. To quantify the effects on proliferation by GABAA receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABAA receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABAA receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl–transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABAA receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABAA receptors. This supported the depolarising role for the GABAA receptors. Inhibition of L-type voltage-gated Ca2+ channels (VGCCs) reduced the proliferation in the same way as inhibition of the GABAA receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27KIP1, along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27KIP1 after inhibition of either the GABAA receptors or the L-type VGCCs suggests a link between the GABAA receptors, membrane potential, and intracellular Ca2+ in regulating the cell cycle

Spontaneously opening GABA receptors play a significant role in neuronal signal filtering and integration

Acknowledgements This work was supported by The Rosetrees Trust Research Grant A1066, RS MacDonald Seedcorn Award and Wellcome Trust—UoE ISSF Award to S.S. The authors thank Prof. David Wyllie (University of Edinburgh) and Prof. Dmitri Rusakov (UCL) for their valuable suggestions on paper preparation.Peer reviewedPublisher PD

Échangeurs d’ions bidimensionnels

L’étude expérimentale des lois cinétiques de la réaction d’échange des ions POCl62-/C1-, réaction effectuée par trois échangeurs d’ions bidimensionnels, et l’interprétation des résultats obtenus montrent que ce processus est régi par la diffusion des ions PoCl62- dans une couche macroscopique d’une épaisseur égale à environ 0,4 mm, du milieu liquide adjacent aux échangeurs. Ceux-ci sont constitués par les couches monomoléculaires des savons suivants : les chlorures d’hexadécyl- triméthylammonium, hexadécylpyridinium et hexadécyl- éthyloldiméthylammonium, adsorbés à la surface du milieu aqueux qui contient les deux ions PoCl62- et Cl-

Apport de la clozapine dans le trouble bipolaire (à propos d'un cas de trouble bipolaire à cycles rapides)

La forme à cycles rapides est une modalité évolutive du trouble bipolaire particulièrement difficile à prendre en charge et fréquemment responsable de résistance aux traitements. La clozapine, chef de file des antipsychotiques atypiques, représente une alternative thérapeutique prometteuse bien que n'ayant pas d'autorisation officielle de mise sur le marché dans cette indication. De nombreuses études, malgré des faiblesses méthodologiques avérées, ont en effet suggéré une efficacité curatrice et prophylactique de cet agent dans le trouble bipolaire, notamment dans les formes à cycles rapides. Les effets secondaires hématologiques, potentiellement létaux, en limitent cependant l'usage, qui doit être essentiellement réservé aux formes résistantes dans un cadre légal strict de prescription. La mise en place d'études aux stratégies plus rigoureuses pourrait permettre dans l'avenir de confirmer l'action thymorégulatrice de la clozapine et permettre un élargissement de ses indications.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Étude comparative du valganciclovir (Rovalcyte®) et du valaciclovir (Zélitrex®) dans la prévention de la maladie à cytomégalovirus en transplantation rénale

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Comment apporter des calories supplémentaires à une personne âgée malade et dénutrie ?

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF