1,720,963 research outputs found
Direct autocrine inhibition and cAMP-dependent potentiation of single L-type Ca2+ channels in bovine chromaffin cells.
No full textBrain-derived neurotrophic factor enhances GABA release probability and nonuniform distribution of N- and P/Q-type channels on release sites of hippocampal inhibitory synapses.
No full textLong-lasting exposures to brain-derived neurotrophic factor (BDNF) accelerate the functional maturation of GABAergic transmission in
embryonic hippocampal neurons, but the molecular bases of this phenomenon are still debated. Evidence in favor of a postsynaptic site
of action has been accumulated, but most of the data support a presynaptic site effect. A crucial issue is whether the enhancement of
evoked IPSCs (eIPSCs) induced by BDNF is attributable to an increase in any of the elementary parameters controlling neurosecretion,
namely the probability of release, the number of release sites, the readily releasable pool (RRP), and the quantal size.
Here, using peak-scaled variance analysis of miniature IPSCs, multiple probability fluctuation analysis, and cumulative amplitude
analysis of action potential-evoked postsynaptic currents, we show that BDNF increases release probability and vesicle replenishment
with little or no effect on the quantal size, the number of release sites, the RRP, and the Ca2 dependence of eIPSCs. BDNF treatment
changes markedly the distribution of Ca2 channels controlling neurotransmitter release. It enhances markedly the contribution of Nand
P/Q-type channels, which summed to100% (“supra-additivity”), and deletes the contribution of R-type channels. BDNF accelerates
the switch of presynaptic Ca2 channel distribution from “segregated” to “nonuniform” distribution. This maturation effect was
accompanied by an uncovered increased control of N-type channels on paired-pulse depression, otherwise dominated by P/Q-type
channels in untreated neurons. Nevertheless, BDNF preserved the fast recovery from depression associated with N-type channels. These
novel presynaptic BDNF actions derive mostly from an enhanced overlapping and better colocalization of N- and P/Q-type channels to
vesicle release sites.
Key words: neurotrophin
G-protein- and cAMP-dependent L-channel gating modulation: a manyfold system to control calcium entry in neurosecretory cells.
No full textBDNF up-regulates evoked GABAergic transmission in developing hippocampus by potentiating presynaptic N- and P/Q-type Ca2+ channels signalling.
No full textOpposite action of beta1- and beta2-adrenergic receptors on Ca(V)1 L-channel current in rat adrenal chromaffin cells.
No full textVoltage-gated Ca2+ channels of chromaffin cells are modulated by locally released neurotransmitters through autoreceptor-activated G-proteins. Clear evidence exists in favor of a Ca2+ channel gating inhibition mediated by purinergic, opioidergic, and α-adrenergic autoreceptors. Few and contradictory data suggest also a role of β-adrenergic autoreceptors (β-ARs), the action of which, however, remains obscure. Here, using patch-perforated recordings, we show that rat chromaffin cells respond to the β-AR agonist isoprenaline (ISO) by either upmodulating or downmodulating the amplitude of Ca2+ currents through two distinct modulatory pathways. ISO (1 μm) could cause either fast inhibition (∼25%) or slow potentiation (∼25%), or a combination of the two actions. Both effects were completely prevented by propranolol. Slow potentiation was more evident in cells pretreated with pertussis toxin (PTX) or when β1-ARs were selectively stimulated with ISO + ICI118,551. Potentiation was absent when the β2-AR-selective agonist zinterol (1 μm), the protein kinase A (PKA) inhibitor H89, or nifedipine was applied, suggesting that potentiation is associated with a PKA-mediated phosphorylation of L-channels (∼40% L-current increase) through β1-ARs. The ISO-induced inhibition was fast and reversible, preserved in cell treated with H89, and mimicked by zinterol. The action of zinterol was mostly on L-channels (38% inhibition). Zinterol action preserved the channel activation kinetics, the voltage-dependence of theI–V characteristic, and was removed by PTX, suggesting that β2AR-mediated channel inhibition was mainly voltage independent and coupled to Gi/Go-proteins. Sequential application of zinterol and ISO mimicked the dual action (inhibition/potentiation) of ISO alone. The two kinetically and pharmacologically distinct β-ARs signaling uncover alternative pathways, which may serve the autocrine control of Ca2+-dependent exocytosis and other related functions of rat chromaffin cells
Direct and remote modulation of L-channels in chromaffin cells: distinct actions on alpha1C and alpha1D subunits
No full textUnderstanding precisely the functioning of voltage-gated Ca2+ channels and their modulation by signaling molecules will help clarifying the Ca(2+)-dependent mechanisms controlling exocytosis in chromaffin cells. In recent years, we have learned more about the various pathways through which Ca2+ channels can be up- or down-modulated by hormones and neurotransmitters and how these changes may condition chromaffin cell activity and catecolamine release. Recently, the attention has been focused on the modulation of L-channels (CaV 1), which represent the major Ca2+ current component in rat and human chromaffin cells. L-channels are effectively inhibited by the released content of secretory granules or by applying mixtures of exogenous ATP, opioids, and adrenaline through the activation of receptor-coupled G proteins. This unusual inhibition persists in a wide range of potentials and results from a direct (membrane-delimited) interaction of G protein subunits with the L-channels co-localized in membrane microareas. Inhibition of L-channels can be reversed when the cAMP/PKA pathway is activated by membrane permeable cAMP analog or when cells are exposed to isoprenaline (remote action), suggesting the existence of parallel and opposite effects on L-channel gating by distinctly activated membrane autoreceptors. Here, the authors review the molecular components underlying these two opposing signaling pathways and present new evidence supporting the presence of two L-channel types in rat chromaffin cells (alpha1C and alpha1D), which open new interesting issues concerning Ca(2+)-channel modulation. In light of recent findings on the regulation of exocytosis by Ca(2+)-channel modulation, the authors explore the possible role of L-channels in the autocontrol of catecholamine release
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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