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Caratterizzazione molecolare e funzionale del canale HCN4 nel nodo senoatriale di coniglio
No full textMolecular and functional characterisation of the HCN4 channel in rabbit sinoatrial node The cardiac sinoatrial node (SAN) is composed of specialised myocytes that generate the spontaneous electrical activity responsible for the cardiac rhythm. This automaticity relies on the spontaneous slow depolarization (pacemaker potential), which at the end of an action potential drives the membrane potential to the threshold for a new event. The most important contribution to the net inward current flowing during this pacemaker potential comes from the activation of the If current. We characterised the principal f channels molecular constituent, HCN4 (Hyperpolarization-activated Cyclic Nucleotide-gated) channel, identified as the most important in the rabbit SAN. In the present work, we used immunofluorescence and western blot analysis to reveal the expression of HCN4 protein and in situ hybridisation to reveal the expression of HCN4 mRNA. There was a strong correlation between HCN4 mRNA and protein expression in the intercaval region, the same region from which pacemaker activity can be recorded. We also delineated the HCN4 distribution in the entire tissue and, with gene silencing experiments, we demonstrated that this isoform is functionally the major constituent of the pacemaker channel. In conclusion, this work shows that HCN4 is a specific marker of the natural cardiac pacemaker, interesting and important result in perspective to realising a biological pacemaker
siRNA-mediated knock-down of the HCN4 gene in cultured rabbit neonatal SAN cells
No full textsiRNA-mediated knock-down of the HCN4 gene in cultured rabbit neonatal SAN cell
Localization of f-channels to caveolae mediates specific beta(2)-adrenergic receptor modulation of rate in sinoatrial myocytes
No full textbeta(1)- and beta(2)-adrenergic receptors (ARs) coexist in different regions of the heart. The beta(2)/beta(1) expression ratio is higher in the sinoatrial node (SAN) than in atria and ventricles, but the specific contribution of either type of receptor to rate modulation is still not well established. We have recently demonstrated that pacemaker ("funny") f-channels are located in lipid rafts of the rabbit SAN. Since in ventricular myocytes beta(2)-, but not beta(1)-ARs, localize to caveolae, we hypothesized that modulation of f-channels and of pacemaker activity in SAN myocytes is controlled mainly by beta(2)-AR activation. To address this point, we investigated the caveolar localization of proteins by co-immunoprecipitation and immunocytochemistry, and found that f-channels interact with caveolin 3. We also recorded If current and spontaneous activity from SAN myocytes, and found that beta-AR activation by the non-selective agonists isoproterenol and fenoterol shifted the If activation curve similarly (by 6.3 and 5.3 mV) and increased similarly spontaneous rate (by 23.1% and 21.6%, respectively). Specific 2 stimulation had similar effects (4.9 mV shift of the activation curve and 16.9% rate increase), but specific 0 1 stimulation was less effective (1.7 mV shift and 7.2% rate increase). However, after caveolar disorganization by M beta CD (2%), stimulation of beta(1)-ARs was as effective as non-specific -AR stimulation. These data show that specific stimulation of beta(2)-ARZs is the main mechanism by which heart rate is modulated through a positive shift of the If activation curve and that this mechanism requires specific membrane compartmentation
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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