1,720,962 research outputs found
alpha(1E) subunits form the pore of three cerebellar R-type calcium channels with different pharmacological and permeation properties
No full textR-type Ca(2+) channels cooperate with P/Q- and N-type channels to control neurotransmitter release at central synapses. The leading candidate as pore-forming subunit of R-type channels is the alpha(1E) subunit. However, R-type Ca(2+) currents with permeation and/or pharmacological properties different from those of recombinant Ca(2+) channels containing alpha(1E) subunits have been described, and therefore the molecular nature of R-type Ca(2+) channels remains not completely settled. Here, we show that the R-type Ca(2+) current of rat cerebellar granule cells consists of two components inhibited with different affinity by the alpha(1E) selective antagonist SNX482 (IC(50) values of 6 and 81 nM) and a third component resistant to SNX482. The SNX482-sensitive R-type current shows the unique permeation properties of recombinant alpha(1E) channels; it is larger with Ca(2+) than with Ba(2+) as charge carrier, and it is highly sensitive to Ni(2+) block and has a voltage-dependence of activation consistent with that of G2 channels with unitary conductance of 15 pS. On the other hand, the SNX482-resistant R-type current shows permeation properties similar to those of recombinant alpha(1A) and alpha(1B) channels; it is larger with Ba(2+) than with Ca(2+) as charge carrier(,) and it has a low sensitivity to Ni(2+) block and a voltage-dependence of activation consistent with that of G3 channels with unitary conductance of 20 pS. Gene-specific knock-down by antisense oligonucleotides demonstrates that the different cerebellar R-type channels are all encoded by the alpha(1E) gene, suggesting the existence of alpha(1E) isoforms with different pore properties
Functional diversity of P-type and R-type calcium channels in rat cerebellar neurons
No full textBy combining single-channel and whole-cell patch-clamp recordings, we have established the sensitivity to omega-agatoxin IVA and omega-conotoxin MVIIC (SNX-230) of G1, G2, and G3, the three novel non-L-, non-N-type Ca2- channels characterized previously in rat cerebellar granule cells. G1 channels were blocked irreversibly by both omega-conotoxin MVIIC and low doses of omega-agatoxin IVA (saturation at 50 nM). Thus, according to pharmacological criteria, G1 channels must be classified as P-type Ca2+ channels. Being slowly inactivating during depolarizing pulses and completely inactivated at voltages in which steady-state inactivation of P-type channels in Purkinje cells is negligible, G1 represents a novel P subtype. Neither G2 nor G3 was blocked irreversibly by omega-conotoxin MVIIC, and therefore both are R-type Ca2+ channels. G2 and G3 have some biophysical properties similar to those of low-voltage-activated (LVA) Ca2- channels (e.g., voltage range for steady-state inactivation. V-1/2 = -90 mV), some properties similar to those of high-voltage-activated (HVA) Ca2+ channels (e.g., high sensitivity to Cd2+ block), and other properties intermediate between those of LVA and HVA Ca2+ channels, with LVA properties prevailing in G2 and HVA properties prevailing in G3. The R-type whole-cell current was inhibited by Ni2+ with a biphasic dose-response curve (IC50: 4 and 153 mu M), suggesting that G2 and G3 may have a different sensitivity to Ni2+ block. Our results uncover functional diversity of both native P-type and R-type Ca2+ channels and show that R subtypes with distinct biophysical properties are coexpressed in rat cerebellar granule cells
Three novel types of voltage-dependent calcium channels in rat cerebellar neurons
No full textWith the aim of characterizing the functional and pharmacological properties of the different voltage-dependent Ca2+ channels expressed in a given type of CNS neuron, we obtained single Ca2+ channel recordings from rat cerebellar granule cells in primary culture. Our data show that three novel classes of voltage-dependent Ca2+ channels are coexpressed in cerebellar granule cells. They are pharmacologically distinct from dihydropyridine-sensitive L-type and omega-conotoxin-sensitive N-type channels, and their functional properties are different from those of P- and T-type channels. The three novel 21 pS G1-, 15 pS G2-, and 20 pS G3-type Ca2+ channels have similar inactivation properties. They show complete steady-state inactivation at -40 mV and their single-channel average currents have both sustained and decaying components. They differ in activation threshold (-40 mV for G2, -30 mV for G3, and -10 mV for G1, with 90 mM Ba2+ as charge carrier), mean open time (1.2 msec for G2, 1 msec for G3, 0.8 msec for G1), and single-channel currents (at 0 mV: 0.5 pA for G2, 0.8 pA for G3, and 1.4 pA for G1). Together with the previously characterized multiple L-type Ca2+ channels (Forti and Pietrobon, 1993), G1-, G2-, and G3-type channels constitute the large majority of Ca2+ channels of cerebellar granule cells in culture. The low activation threshold of G2-type channels and their inactivation properties suggest that they might be native counterparts of the recently expressed rat brain clone rbE-II (Soong et al., 1993)
G2 and G3: Two different R-Type (toxin-resistant) calcium channels coexpressed in rat cerebellar granule cells", in "Low-voltage activated T-type Calcium channels
No full text"G2 and G3: two different R-type (toxin resistant) calcium channels coexpressed in rat cerebellar granule cells."
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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