Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels

Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K+ channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the “helix-bundle crossing”. However, in the inwardly rectifying (Kir) potassium channel family, the role of this “hinge” residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper “hinge” residues are in close contact with the base of the pore α-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the “lower” gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue

AMPA Receptors Commandeer an Ancient Cargo Exporter for Use as an Auxiliary Subunit for Signaling

Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a proteomic approach, two homologues of the cargo exporter cornichon, CNIH-2 and CNIH-3, have recently been identified as constituents of native AMPARs in mammalian brain. In heterologous reconstitution experiments, CNIH-2 promotes surface expression of GluAs and modulates their biophysical properties. However, its relevance in native AMPAR physiology remains controversial. Here, we have studied the role of CNIH-2 in GluA processing both in heterologous cells and primary rat neurons. Our data demonstrate that CNIH-2 serves an evolutionarily conserved role as a cargo exporter from the endoplasmic reticulum (ER). CNIH-2 cycles continuously between ER and Golgi complex to pick up cargo protein in the ER and then to mediate its preferential export in a coat protein complex (COP) II dependent manner. Interaction with GluA subunits breaks with this ancestral role of CNIH-2 confined to the early secretory pathway. While still taking advantage of being exported preferentially from the ER, GluAs recruit CNIH-2 to the cell surface. Thus, mammalian AMPARs commandeer CNIH-2 for use as a bona fide auxiliary subunit that is able to modify receptor signaling

Pitfalls and complications in the treatment of cervical spine fractures in patients with ankylosing spondylitis

Patients with ankylosing spondylitis are at significant risk for sustaining cervical spine injuries following trauma predisposed by kyphosis, stiffness and osteoporotic bone quality of the spine. The risk of sustaining neurological deficits in this patient population is higher than average. The present review article provides an outline on the specific injury patterns in the cervical spine, diagnostic algorithms and specific treatment modalities dictated by the underlying disease in patients with ankylosing spondylitis. An emphasis is placed on the risks and complication patterns in the treatment of these rare, but challenging injuries

Missed foot fractures in polytrauma patients: a retrospective cohort study

BACKGROUND: Missed foot fractures are a known problem in the care of the traumatized patient. They do not usually have an influence on the survival, but on the long-term result and the quality of the patient''s life. The aim of this study is to find out how many of these fractures are overlooked in a Level I trauma center and what the consequences for the patients are hypothesing that patients with a delayed diagnosis will have worse clinical results. METHODS: Forty-seven patients (7.3%) with foot fractures could be identified in 642 polytrauma patients, retrospectively. All patients were divided into two groups: early diagnosed fractures and delayed diagnosed fractures, the latter defined as diagnosed after Secondary Survey. Patients were evaluated according to the Hannover Outcome Score, the Short Form-36 Health Survey, the AOFAS Score and the Hannover Scoring System. The average follow-up was 5 years and 8 months. Reasons for overlooking a foot fracture were analyzed. RESULTS: The foot fracture was early diagnosed in 26 (55.3%) patients, but delayed in 21 (44.7%). There were no significant differences in the mean stay in the hospital or in the ICU. The fractures that were most often missed were those of the cuboid or the metarsalia. The highest risk factor for a delayed diagnosis was a fracture already diagnosed on the same foot. In 52.4% of the delayed diagosed fractures, an operative therapy was necessary. There were no significant differences between the two groups in the clinical results. CONCLUSIONS: In summary, the results of this study show that foot injuries can be a safety problem for the patient and the examination of the feet in the trauma room has to be a compulsory part of the algorithm. Although the majority of delayed diagnosed foot fractures demonstrated comparable results to the immediately diagnosed fractures, approximately 10% might have benefited from an earlier diagnosis. Even if there were no significant differences in the clinical results, we have to be aware that missing a fracture in the foot can lead to worse results in the complete polytrauma care

Missed foot fractures in polytrauma patients: a retrospective cohort study

BACKGROUND: Missed foot fractures are a known problem in the care of the traumatized patient. They do not usually have an influence on the survival, but on the long-term result and the quality of the patient''s life. The aim of this study is to find out how many of these fractures are overlooked in a Level I trauma center and what the consequences for the patients are hypothesing that patients with a delayed diagnosis will have worse clinical results. METHODS: Forty-seven patients (7.3%) with foot fractures could be identified in 642 polytrauma patients, retrospectively. All patients were divided into two groups: early diagnosed fractures and delayed diagnosed fractures, the latter defined as diagnosed after Secondary Survey. Patients were evaluated according to the Hannover Outcome Score, the Short Form-36 Health Survey, the AOFAS Score and the Hannover Scoring System. The average follow-up was 5 years and 8 months. Reasons for overlooking a foot fracture were analyzed. RESULTS: The foot fracture was early diagnosed in 26 (55.3%) patients, but delayed in 21 (44.7%). There were no significant differences in the mean stay in the hospital or in the ICU. The fractures that were most often missed were those of the cuboid or the metarsalia. The highest risk factor for a delayed diagnosis was a fracture already diagnosed on the same foot. In 52.4% of the delayed diagosed fractures, an operative therapy was necessary. There were no significant differences between the two groups in the clinical results. CONCLUSIONS: In summary, the results of this study show that foot injuries can be a safety problem for the patient and the examination of the feet in the trauma room has to be a compulsory part of the algorithm. Although the majority of delayed diagnosed foot fractures demonstrated comparable results to the immediately diagnosed fractures, approximately 10% might have benefited from an earlier diagnosis. Even if there were no significant differences in the clinical results, we have to be aware that missing a fracture in the foot can lead to worse results in the complete polytrauma care

Effets des stimulations buccofaciales et du support oral sur la succion et la déglutition du nouveau-né prématuré

Le but de l'étude était d'appliquer, dans le même protocole, chez le prématuré, les programmes de stimulation orale (Stim) et de support oral (Sup), d'évaluer et de comparer leurs effets sur la déglutition par la technique acoustique et sur la succion non nutritive (SNN) par la technique de succiométrie. Sup réduit la période de transition, mais mais pas Stim. Sup est le programme le plus efficace sur l'ingestion et la déglutition : Sup stabilise la mâchoire, aide à la déglutition, rythme déglutition-respiration, développe l'endurance. Stim augmente tous les paramètres de SNN pendant l'alimentation par sonde. Pendant la transition, ces paramètres se stabilisent avec Stim et augmentent avec Sup et ne permettent pas de différencier stim et Sup. Les paramètres de déglutition évalués par la technique acoustique non invasive permettent de différencier Stim et Sup. Ainsi, Sup peut être considéré comme un programme d'entraînement à l'endurance et à la coordination succion-déglutition-respiration.The aim of the study was to perform, in the same protocol, oral stimulation (Stim) and oral support (Sup) programs, to quantify and to compare its effects on swallowing with the non invasive acoustic technique and non nutritive sucking (NSS) with succiometry, in preterm infants. The transition is reduced with Sup but not with Stim. Sup is the most efficient program on feeding performances and swallowing : Sup stabilizes the jaw, is a aid to deglutition, imposes a rythm between swallowing and breathing, enhances endurance. NSS parameters are increased with Stim during the feeding. During transition, these NNS parameters are stabilized with Stim and are enhanced with Sup, but cannot separated Stim and Sup. Swallowing parameters are evaluated with the non invasive acoustic technique and can distinguish Stim and Sup. Moreover, Sup can be applied as a training for endurance and sucking-swallowing-breathing coordination.TOURS-BU Médecine (372612103) / SudocSudocFranceF