Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier

AbstractVoltage-dependent sodium (Na+) channels are highly concentrated at nodes of Ranvier in myelinated axons and play a key role in promoting rapid and efficient conduction of action potentials by saltatory conduction. The molecular mechanisms that direct their localization to the node are not well understood but are believed to involve contact-dependent signals from myelinating Schwann cells [1] and interactions of Na+ channels with the cytoskeletal protein, ankyrin G [2]. Two cell adhesion molecules (CAMs) expressed at the axon surface, Nr-CAM and neurofascin, are also linked to ankyrin G and accumulate at early stages of node formation, suggesting that they mediate contact-dependent Schwann cell signals to initiate node development [3]. To examine the potential role of Nr-CAM in this process, we treated myelinating cocultures of DRG (dorsal root ganglion) neurons and Schwann cells with an Nr-CAM-Fc (Nr-Fc) fusion protein. Nr-Fc had no effect on initial axon-Schwann cell interactions, including Schwann cell proliferation, or on the extent of myelination, but it strikingly and specifically inhibited Na+ channel and ankyrin G accumulation at the node. Nr-Fc bound directly to neurons and clustered and coprecipitated neurofascin expressed on axons. These results provide the first evidence that neurofascin plays a major role in the formation of nodes, possibly via interactions with Nr-CAM

Genetic defects in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations

Myelination

International audienceMyelin is a key evolutionary acquisition that underlay the development of the large, complex nervous systems of all hinged-jaw vertebrates. By promoting rapid, efficient nerve conduction, myelination also made possible the development of the large body size of these vertebrates. In addition to increasing the speed of nerve conduction, myelination has emerged as a source of plasticity in neural circuits that is crucial for proper timing and function. Here, we briefly describe the organization of myelin and of myelinated axons, as well as the functions of myelin in nerve conduction and neural circuits, and consider its potential evolutionary origins

Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia.

BACKGROUND: /st> Neuraxial anaesthesia improves tissue perfusion and tissue oxygen tension. Vasodilation induced by this technique may result in hypotension requiring the administration of vasoactive drugs. The use of peripheral vasoconstrictors might counteract the improved tissue perfusion and its potentially beneficial effects. We therefore investigated the effect of i.v. norepinephrine and ephedrine on skin perfusion using laser-Doppler flowmetry (LDF) in patients during spinal anaesthesia. METHODS: /st> Skin blood flow expressed in perfusion units (PU) provided by LDF was measured simultaneously at the foot and the manubrium levels in 44 patients during spinal anaesthesia with a sensory level below T5. Norepinephrine infusion was then titrated to normalize mean arterial pressure (MAP) in 23 patients (Group NOR). Ephedrine (max. 10 mg) was administered in 21 patients (Group EPH). Changes in relative PU were compared between the two sites of measurements in each group during drug administration. The same doses of norepinephrine were assessed in 11 normal volunteers to assure comparable vasoreactivity at the foot and manubrium levels. RESULTS: /st> Spinal anaesthesia resulted in a 10% decrease in MAP (P Improved skin perfusion induced by spinal anaesthesia was not counteracted by the use of norepinephrine or ephedrine