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International audienc

Calcium currents in striatal fast-spiking interneurons: dopaminergic modulation of CaV1 channels

Abstract Background Striatal fast-spiking interneurons (FSI) are a subset of GABAergic cells that express calcium-binding protein parvalbumin (PV). They provide feed-forward inhibition to striatal projection neurons (SPNs), receive cortical, thalamic and dopaminergic inputs and are coupled together by electrical and chemical synapses, being important components of the striatal circuitry. It is known that dopamine (DA) depolarizes FSI via D1-class DA receptors, but no studies about the ionic mechanism of this action have been reported. Here we ask about the ion channels that are the effectors of DA actions. This work studies their Ca2+ currents. Results Whole-cell recordings in acutely dissociated and identified FSI from PV-Cre transgenic mice were used to show that FSI express an array of voltage gated Ca2+ channel classes: CaV1, CaV2.1, CaV2.2, CaV2.3 and CaV3. However, CaV1 Ca2+ channel carries most of the whole-cell Ca2+ current in FSI. Activation of D1-like class of DA receptors by the D1-receptor selective agonist SKF-81297 (SKF) enhances whole-cell Ca2+ currents through CaV1 channels modulation. A previous block of CaV1 channels with nicardipine occludes the action of the DA-agonist, suggesting that no other Ca2+ channel is modulated by D1-receptor activation. Bath application of SKF in brain slices increases the firing rate and activity of FSI as measured with both whole-cell and Ca2+ imaging recordings. These actions are reduced by nicardipine. Conclusions The present work discloses one final effector of DA modulation in FSI. We conclude that the facilitatory action of DA in FSI is in part due to CaV1 Ca2+ channels positive modulation

Économie sociale et solidaire et État

L’économie sociale et solidaire (ESS) possède sa dynamique propre. En tant que forme d’économie, elle contrebalance les échecs du marché et les limites de l’État et c’est à ce double titre qu’elle prend une place grandissante dans la réflexion des universitaires et des décideurs publics. Elle s’appuie néanmoins sur la longue histoire de l’associationnisme qui passe par l’invention d’institutions de protection sociale (mutuelles, associations caritatives, …) et la définition de politiques sociales (aide à domicile, handicap, insertion, …) pour aboutir au système français actuel. À ce titre, l’ESS est un instrument disponible pour renouveler les modes d’élaboration des politiques publiques et de délivrance des services publics introduisant du partenariat entre l’État et l’ESS afin de dynamiser et de réorienter l’action publique. Différents scenarios ont déjà été éprouvés : entre complémentarité et substitution, entre partenariat et affrontement dans le domaine de la protection sociale en France. Les enjeux sont de taille, et la question de l’évaluation de l’ESS présente le risque d’être standardisée. La coopération entre ESS et biens communs, ces derniers véhiculent des valeurs communes d’universalité et de partage, offre également des potentialités non négligeables. Plusieurs études de cas sont présentées dans l’ouvrage. En Russie, au Danemark, au Québec, et en France, la diversité des rapports entre État et ESS est abordée : concurrence, volontariat, co-production et biens communs. D’autres exemples (Suède, Espagne, Grande-Bretagne et Pays-Bas) démontrent le potentiel d’innovation que représentent les relations État, secteur privé et l’économie sociale et solidaire

Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Introduction: In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods: We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results: Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion: In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment