73 research outputs found
Implication du cotransporteur potassium-chlorure de type 3 dans la régulation de la pression artérielle chez la souris
Le cotransporteur K+-Cl− de type 3 (KCC3) est un transporteur d’ions qui fait partie de la famille des cotransporteurs cation-Cl− et qui serait impliqué dans la régulation de la pression artérielle (PA). Pour comprendre comment il accomplit son rôle, nous avons procédé à la caractérisation détaillée du phénotype cardiovasculaire d’un modèle murin Kcc3−/−. Nous avons observé que ce modèle se distinguait de la souris type sauvage par une PA pulsée et une fréquence cardiaque plus basses, une PA diastolique plus élevée, une aorte isolée moins réactive à la stimulation adrénergique, une masse ventriculaire augmentée, une aldostéronémie plus élevée sans suppression de la rénine et divers troubles neurologiques. Ces données suggèrent que les désordres hémodynamiques chez la souris Kcc3−/− sont causés en partie par l’absence de KCC3 dans la paroi de différents types de vaisseaux, ce qui entraînerait une augmentation de la résistance vasculaire périphérique et de la distensibilité aortique.The K+-Cl− cotransporter type 3 (KCC3) is an ion transporter that belongs to the cation-Cl− cotransporter family and that probably plays an important role in blood pressure (BP) regulation. To determine how it accomplishes this role more specifically, we have characterized the cardiovascular phenotype of a Kcc3−/− mouse model through detailed analyses. We have found that this model distinguished itself from the wild-type animals by lower pulse pressure and heart rate, higher diastolic BP, lower in vitro reactivity of their aorta to adrenergic stimulation, higher ventricular mass, higher aldosterone levels in the absence of renin suppression and various neurologic abnormalities. These observations suggest that the hemodynamic disorders identified in the Kcc3−/− mouse model are due in part to the absence of KCC3 in the wall of different vessel types, leading to higher peripheral vascular resistance and aortic distensibility
Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters
Potassium-coupled chloride transporters (KCCs) play crucial roles
in regulating cell volume and intracellular chloride concentration.
They are characteristically inhibited under isotonic conditions via
phospho-regulatory sites located within the cytoplasmic termini.
Decreased inhibitory phosphorylation in response to hypotonic cell
swelling stimulates transport activity, and dysfunction of this
regulatory process has been associated with various human
diseases. Here, we present cryo-EM structures of human KCC3b
and KCC1, revealing structural determinants for phosphoregulation in both N- and C-termini. We show that phosphomimetic KCC3b is arrested in an inward-facing state in which
intracellular ion access is blocked by extensive contacts with the
N-terminus. In another mutant with increased isotonic transport
activity, KCC1D19, this interdomain interaction is absent, likely
due to a unique phospho-regulatory site in the KCC1 N-terminus.
Furthermore, we map additional phosphorylation sites as well as a
previously unknown ATP/ADP-binding pocket in the large Cterminal domain and show enhanced thermal stabilization of
other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and
may unlock innovative strategies for drug development
Calibrated ages of KUJU (BF2) peat core from Canada
Calibrated ages of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project
Age determination of KUJU (BF2) peat core from Canada
14C and 210Pb age determination of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project
Age determination of KUJU (PD2) peat core from Canada
14C and 210Pb age determination of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project
Calibrated ages of KUJU (PD2) peat core from Canada
Calibrated ages of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project
Geochemistry of KUJU (BF2) peat core from Canada
Geochemistry data of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project
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