The Experts below are selected from a list of 14787 Experts worldwide ranked by ideXlab platform

Raynald Laprade - One of the best experts on this subject based on the ideXlab platform.

Mark Farrant - One of the best experts on this subject based on the ideXlab platform.

  • adaptive regulation of neuronal excitability by a voltage independent Potassium Conductance
    Nature, 2001
    Co-Authors: Stephen G Brickley, Victoria Revilla, S G Cullcandy, William Wisden, Mark Farrant
    Abstract:

    Many neurons receive a continuous, or 'tonic', synaptic input, which increases their membrane Conductance, and so modifies the spatial and temporal integration of excitatory signals. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma-aminobutyric acid) gives rise to a persistent Conductance mediated by the GABA A receptor that also modifies the excitability of granule cells. Here we show that this tonic Conductance is absent in granule cells that lack the alpha6 and delta-subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a 'leak' Conductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K + Conductance that maintains normal neuronal behaviour.

  • adaptive regulation of neuronal excitability by a voltage independent Potassium Conductance
    Nature, 2001
    Co-Authors: Stephen G Brickley, Victoria Revilla, S G Cullcandy, William Wisden, Mark Farrant
    Abstract:

    Many neurons receive a continuous, or ‘tonic’, synaptic input, which increases their membrane Conductance, and so modifies the spatial and temporal integration of excitatory signals1,2,3. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (γ-aminobutyric acid)4 gives rise to a persistent Conductance mediated by the GABA A receptor5,6,7 that also modifies the excitability of granule cells8. Here we show that this tonic Conductance is absent in granule cells that lack the α6 and δ-subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a ‘leak’ Conductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K+ Conductance that maintains normal neuronal behaviour.

Macdonald J Christie - One of the best experts on this subject based on the ideXlab platform.

  • how opioids inhibit gaba mediated neurotransmission
    Nature, 1997
    Co-Authors: Christopher W Vaughan, Mark Connor, Susan L Ingram, Macdonald J Christie
    Abstract:

    The midbrain region periaqueductal grey (PAG) is rich in opioid receptors and endogenous opioids and is a major target of analgesic action in the central nervous system. It has been proposed that the analgesic effect of opioids on the PAG works by suppressing the inhibitory influence of the neurotransmitter GABA (gamma-aminobutyric acid) on neurons that form part of a descending antinociceptive pathway. Opioids inhibit GABA-mediated (GABAergic) synaptic transmission in the PAG and other brain regions by reducing the probability of presynaptic neurotransmitter release, but the mechanisms involved remain uncertain. Here we report that opioid inhibition of GABAergic synaptic currents in the PAG is controlled by a presynaptic voltage-dependent Potassium Conductance. Opioid receptors of the mu type in GABAergic presynaptic terminals are specifically coupled to this Potassium Conductance by a pathway involving phospholipase A2, arachidonic acid and 12-lipoxygenase. Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products. These mechanisms account for the analgesic action of cyclooxygenase inhibitors in the PAG and their synergism with opioids.

  • nociceptin receptor coupling to a Potassium Conductance in rat locus coeruleus neurones in vitro
    British Journal of Pharmacology, 1996
    Co-Authors: Mark Connor, Christopher W Vaughan, Billy Chieng, Macdonald J Christie
    Abstract:

    1. In this study we have examined the effects of nociceptin, an endogenous ligand for the opioid-like receptor ORL1 on the membrane properties of rat locus coeruleus (LC) neurones in vitro, using intracellular and whole cell patch clamp recording. 2. When locus coeruleus neurones were voltage clamped to -60 mV, application to nociceptin caused an outward current in all cells examined (n = 49), with an EC50 of 90 nM. Neither the potency nor the maximal effect of nociceptin was altered in the presence of the peptidase inhibitors, bestatin (20 microM) or thiorphan (2 microM). 3. The outward currents caused by nociceptin in 2.5 mM extracellular K+ reversed polarity at -123 mV, more negative than the predicted K+ reversal potential of -105 mV. Increasing extracellular K+ to 6.5 mM resulted in a shift of the reversal potential of +25 mV, a shift consistent with a K+ Conductance. The Conductance activated by nociceptin showed mild inward rectification. 4. Application of a high concentration of nociceptin (3 microM) occluded the current produced by simultaneous application of high concentrations of Met-enkephalin (10 microM), (3 microM) somatostatin and UK 14304 (3 microM), indicating that nociceptin activated the same Conductance as mu-opioid and somatostatin receptors and alpha 2-adrenoceptors. 5. The actions of nociceptin were weakly antagonized by the opioid antagonist, naloxone, with pKb's estimated from 2 cells of -4.23 and -4.33. The mu-opioid antagonist, CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Pen-Thr-NH2, 1 microM), the opioid antagonist, nalorphine (30 microM) or the somatostatin antagonist, CPP (cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bz1]) 3 microM) did not affect the nociceptin-induced current. 6. Dynorphin A (microM), another putative endogenous ligand for ORL1, caused a robust outward current in locus coeruleus neurones that was, however, completely antagonized by moderate concentrations of naloxone (300 nM-1 microM). 7. Continuous application of nociceptin (3 microM) resulted in a decrease of the outward current to a steady level of 70% of the maximum response with a t1/2 of 120s. Desensitization was largely homologous because simultaneous application of Met-enkephalin (30 microM) during the desensitized period of the nociceptin response resulted in an outward current that was 92% of control responses to Met-enkephalin in the same cells. Conversely, continuous application of Met-enkephalin (30 microM) resulted in a decrease of Met-enkephalin current to a steady level that was 54% of the initial current. During this desensitized period application of nociceptin (3 microM) resulted in a current that was 78% of the control responses to nociceptin in the same cells. 8. Thus nociceptin potently activates an inwardly rectifying K+ Conductance in locus coeruleus neurones, with a pharmacological profile consistent with activation of the ORL1 receptor. Dynorphin A does not appear to be a ligand for ORL1 in rat locus coeruleus neurones.

Sylvie Breton - One of the best experts on this subject based on the ideXlab platform.

Stephen G Brickley - One of the best experts on this subject based on the ideXlab platform.

  • adaptive regulation of neuronal excitability by a voltage independent Potassium Conductance
    Nature, 2001
    Co-Authors: Stephen G Brickley, Victoria Revilla, S G Cullcandy, William Wisden, Mark Farrant
    Abstract:

    Many neurons receive a continuous, or 'tonic', synaptic input, which increases their membrane Conductance, and so modifies the spatial and temporal integration of excitatory signals. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma-aminobutyric acid) gives rise to a persistent Conductance mediated by the GABA A receptor that also modifies the excitability of granule cells. Here we show that this tonic Conductance is absent in granule cells that lack the alpha6 and delta-subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a 'leak' Conductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K + Conductance that maintains normal neuronal behaviour.

  • adaptive regulation of neuronal excitability by a voltage independent Potassium Conductance
    Nature, 2001
    Co-Authors: Stephen G Brickley, Victoria Revilla, S G Cullcandy, William Wisden, Mark Farrant
    Abstract:

    Many neurons receive a continuous, or ‘tonic’, synaptic input, which increases their membrane Conductance, and so modifies the spatial and temporal integration of excitatory signals1,2,3. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (γ-aminobutyric acid)4 gives rise to a persistent Conductance mediated by the GABA A receptor5,6,7 that also modifies the excitability of granule cells8. Here we show that this tonic Conductance is absent in granule cells that lack the α6 and δ-subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a ‘leak’ Conductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K+ Conductance that maintains normal neuronal behaviour.