69 research outputs found
Terminação de cordeiros em pastagens de azevém anual manejadas em diferentes intensidades e métodos de pastejo
Efeito residual do nitrogĂȘnio na cultura do milho no sistema de produção integração lavoura-pecuĂĄria
Influence of GluN2 subunit identity on NMDA receptor function
AbstractN-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels (âionotropicâ receptors) activated by the major excitatory neurotransmitter, l-glutamate. While the term âthe NMDARâ is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling.This article is part of the Special Issue entitled âGlutamate Receptor-Dependent Synaptic Plasticityâ
Probing spatial and subunit-dependent signalling by the NMDA receptor
NMDARs are ligand-gated cation channels which are activated by the neurotransmitter
glutamate. NMDARs are essential in coupling electrical activity to biochemical
signalling as a consequence of their high Ca2+ permeability. This Ca2+ influx acts as a
secondary messenger to mediate neurodevelopment, synaptic plasticity, neuroprotection
and neurodegeneration. The biological outcome of NMDAR activation is determined by
a complicated interrelationship between the concentration of Ca2+ influx, NMDAR
location (synaptic vs. extrasynaptic) as well as the subtype of the GluN2 subunit. Despite
the recognition that NMDAR mediated physiology is multifaceted, tools used to study
subunit and location dependent signalling are poorly characterized and in other cases,
non-existent. Therefore, the aim of this thesis is to address this issue.
Firstly, I assessed the current pharmacological approach used to selectively activate
extrasynaptic NMDARs. Here, synaptic NMDARs are first blocked with MK-801 during
phasic activation and then extrasynaptic NMDARs are tonically activated. This
approach relies on the continual irreversible blockade of synaptic NMDARs by MK-801
yet contrary to the current dogma, I demonstrate this blockade is unstable during tonic
agonist exposure and even more so when physiologically relevant concentrations of
Mg2+ are present. This confines a temporal limit in which selective activation of
extrasynaptic NMDARs can occur with significant consequences for studying synaptic
vs. extrasynaptic NMDAR signalling.
Dissecting subunit-dependent signalling mediated by the two major GluN2 subunits in
the forebrain, GluN2A and GluN2B, has been advanced significantly by selective
GluN2B antagonism yet a reciprocal GluN2A selective antagonist has been lacking.
Utilizing novel GluN2A-specific antagonists, I demonstrate a developmental
upregulation of GluN2A-mediated NMDA currents which concurrently dilutes the
contribution of GluN2B-mediated currents. Moreover, I tested the hypothesis that the Cterminus
of GluN2A and GluN2B are essential in controlling the developmental switch
of GluN2 subunits utilizing knock-in mice whereby the C-terminus of GluN2A is
replaced with that of GluN2B. Surprisingly, the exchange of the C-terminus does not
impede the developmental switch in subunits nor the proportion of NMDARs at synaptic
vs extrasynaptic sites. However, replacing the C-terminus of GluN2A with that of
GluN2B induces a greater neuronal vulnerability to NMDA-dependent excitotoxicity.
Collectively, this work enhances our understanding of the complex physiology mediated
by the NMDAR by determining how pharmacological tools are best utilized to study the
roles of NMDAR location and subunit composition in addition to revealing the
importance of the GluN2 C-terminus in development and excitotoxicity
Efeitos de diferentes intensidades de pastejo em pastagem nativa melhorada sobre o desempenho animal
Estratégias de manejo da oferta de forragem para recria de novilhas em pastagem natural
Organic Superconductors: when correlations and magnetism walk in
This survey provides a brief account for the start of organic
superconductivity motivated by the quest for high Tc superconductors and its
development since the eighties'. Besides superconductivity found in 1D organics
in 1980, progresses in this field of research have contributed to better
understand the physics of low dimensional conductors highlighted by the wealth
of new remarkable properties. Correlations conspire to govern the low
temperature properties of the metallic phase. The contribution of
antiferromagnetic fluctuations to the interchain Cooper pairing proposed by the
theory is borne out by experimental investigations and supports
supercondutivity emerging from a non Fermi liquid background. Quasi one
dimensional organic superconductors can therefore be considered as simple
prototype systems for the more complex high Tc materials.Comment: 41 pages, 21 figures to be published in Journal of Superconductivity
and Novel Magnetis
VariĂĄveis morfogĂȘnicas de milheto (Pennisetum americanum) mantido em duas alturas de pastejo
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