45 research outputs found

    Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons.

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    Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30-100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional "reporters" for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons

    Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

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    Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

    Tonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons

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    Inhibition is a physiological process that decreases the probability of a neuron generating an action potential. The two main mechanisms that have been proposed for inhibition are hyperpolarization and shunting. Shunting results from increased membrane conductance, and it reduces the neuron-firing probability. Here we show that ambient GABA, the main inhibitory neurotransmitter in the brain, can excite adult hippocampal interneurons. In these cells, the GABAA current reversal potential is depolarizing, making baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Such a biphasic change in interneuron firing leads to corresponding changes in the GABAA-mediated synaptic signalling. The described phenomenon suggests that the excitatory or inhibitory actions of the current are set not only by the reversal potential, but also by the conductance

    Cholinergic Activation of M2 Receptors Leads to Context-Dependent Modulation of Feedforward Inhibition in the Visual Thalamus

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    The temporal dynamics of inhibition within a neural network is a crucial determinant of information processing. Here, the authors describe in the visual thalamus how neuromodulation governs the magnitude and time course of inhibition in an input-dependent way

    Changing the Allocation Rules in the EU ETS: Impact on Competitiveness and Economic Efficiency

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    Rapport VII. c-2. Dynamique d’un canal à eau bouillante

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    This study sets out to determine the criteria governing the critical instability condition for a boiling water channel. A certain number of known analogy models describing such systems are analysed and an improved model presented. The transfer functions for an open circuit are calculated and used to define the conditions under which instability appears in natural-convection or forced-circulation systems. It is shown that the same function determines these conditions in both cases. Hydraulic instability in a forced circulation system is connected with the characteristics of the boiling channel itself, whereas in a natural convection system, the feedback mechanism between the mass flow and vacuum rate plays a very important part. The theoretical results obtained are compared with experimental data from the authors’ laboratory.Le but de cette étude est la détermination des critères pour les seuils d’instabilité d’un canal à eau bouillante. Un certain nombre de modèles analogiques connus décrivant de tels systèmes sont analysés et un modèle amélioré est présenté. Les fonctions de transfert d’un circuit ouvert sont calculées et elles sont utilisées à définir les conditions dans lesquelles les instabilités se présentent dans des systèmes à convection naturelle ou a circulation forcée. On démontre que la même fonction détermine ces conditions dans les deux cas. Dans un système à circulation forcée l’instabilité hydraulique est reliée aux caractéristiques du canal bouillant même, tandis que dans le régime à convection naturelle le mécanisme du «feed-back » entre le débit massique et le taux de vide joue un rôle très important. Les résultats théoriques obtenus sont comparés avec ceux d’expériences exécutées dans ce laboratoire.Verheugen A. N. J., Spigt C. L., Bogaardt M. Rapport VII. c-2. Dynamique d’un canal à eau bouillante. In: Le rôle de la mécanique des fluides dans les progrès récents des techniques. 1967
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