1,720,971 research outputs found
Role of intracellular calcium in fast and slow desensitization of P2-receptors in PC12 cells
No full text1 Combined whole-cell patch clamp recording and confocal laser scanning microscopy of [Ca2+](i) transients were performed on single PC12 cells to study any correlation between membrane currents induced by ATP and elevation in [Ca2+](i). ATP was applied by pressure from micropipettes near the recorded PC12 cells continuously superfused at a fast rate,
2 Brief (20 ms) pulses of ATP elicited monophasic inward currents and [Ca2+](i) increases. Long applications (2 s) of ATP (5 mM) evoked peak currents which rapidly faded during the pulse and were followed by a large rebound current, interpreted as due to rapid desensitization and recovery of P-2-receptors. The associated [Ca2+](i) increase grew monotonically to a peak reached only after the occurrence of the current rebound, indicating that it is unlikely this cation has a role in fast desensitization.
3 Both membrane currents and [Ca2+](i) transients were dependent on holding membrane potential, suggesting that Ca2+ influx is the predominant cause of [Ca2+](i) elevation. Tills view was supported by experiments carried out in Ca2+-free solution.
4 Brief pulses of ATP applied after a desensitizing pulse (2 s) of the same elicited smaller inward currents and [Ca2+](i) rises indicating a role for [Ca2+](i) in controlling slow desensitization of P-2-receptors.
5 This notion was confirmed in experiments with various [Ca2+](i) chelators which differentially affected slow desensitization in relation to their buffering capacity, while sparing fast receptor desensitization,
6 These results suggest a role for [Ca2+](i) in slow rather than fast desensitization of P-2-receptors, thus proposing this divalent cation as an intracellular factor able to provide an efficient and reversible control over receptor activity induced by ATP
The effect of the neuropeptide substance P on desensitization of ATP receptors of PC12 cells
No full text1 Patch clamp recording (whole cell configuration) was employed to investigate the modulatory action of substance P on inward currents elicited by adenosine 5'-triphosphate (ATP, focally applied via a pressure pipette) from phaechromocytoma (PC12) cells usually held at -70 mV.
2 Bath-applied substance P (0.2-20 mu M) had no effect on baseline membrane current but reversibly reduced ATP peak currents in a concentration-dependent fashion. The depressant effect was not associated with a change in the ATP current reversal potential.
3 Equiamplitude peak responses induced by 50 mu M or 5 mM ATP were differentially affected by substance P which preferentially reduced currents evoked by 5 mM ATP. In the presence of substance P a conditioning pulse of ATP evoked a stronger depression to subsequent test pulses of the same agonist.
4 Combined patch clamping and confocal laser imaging of intracellular Ca2+ ([Ca2+](i)) of single PC12 cells showed that substance P (applied by a pressure pipette) pet se had no effect on [Ca2+](i) or current baseline, although it reduced the inward current and associated [Ca2+](i) rise elicited by ATP.
5 These results are interpreted as due to facilitation by substance P of desensitization of ATP-gated P-2X2 receptors of PC12 cells. It is proposed that the novel modulation by this peptide of ATP responses may serve as a model for further studies aimed at elucidating the action of substance P on purinergic neurotransmission
Imaging of intracellular calcium during desensitization of nicotinic acetylcholine receptors of rat chromaffin cells
No full textFading and rebound of currents induced by ATP on PC12 cells
No full text1 Patch clamp recording (whole cell configuration) was used to study the action of ATP on rat phaeochromocytoma (PC12) cells usually held at -70 mV and rapidly superfused with buffered saline. ATP (0.5, 1 or 5 mM), applied from micropipettes by pressure application with brief (less than or equal to 50 ms) pulses, induced inward currents with rapid onset and decay. ADP and alpha,beta-methylene ATP were ineffective.
2 ATP (5 mM) applied with pulses >200 ms long elicited a complex current response characterized by a rapid peak which faded and was followed by a strong current rebound (lasting several s) as soon as the application was terminated. This type of response was readily replicated as long as ATP applications were spaced at 2-3 min intervals. The amplitude of peak and rebound currents was dependent on the length of pressure pulse and was similarly depressed by bath application of a threshold dose (25 mu M) of ATP. Rapid fading and rebound of ATP-induced membrane currents were also observed when the Y-tube method was used for applying this agonist.
3 The reversal potential for peak and rebound currents was the same while the time constant values for peak fading and rebound onset were insensitive to changes in membrane potential between -70 and -40 mV. When ATP was applied to a cell clamped at depolarized potential, no current was observed but rapid return of the membrane potential to -70 mV immediately at the end of ATP application was associated with a large rebound current.
4 Brief (20 ms) application of ATP during the onset of the rebound current strongly and transiently suppressed it. The same application performed during the gradual decay of the rebound wave elicited a transient inward current which was much smaller and shorter than the one observed when the cell was in its resting state. Application of 2 s ATP pulses at 20 s intervals equally reduced the initial peak and rebound currents which recovered at the same rate.
5 The present data are interpreted according to a scheme which suggests two types of ATP receptor desensitization. The first one (D1) would be characterized by fast kinetics and low agonist affinity; rapid recovery from D1 would then be manifested as current rebound presumably due to receptor reactivation. The second desensitized state (D2) has slow kinetics and high affinity for the agonist: it is therefore typically seen with sustained application of a low dose of ATP. It is proposed that desensitization and its recovery can influence the time course of membrane responses mediated by purinoceptors
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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