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      Effect of α-Allocryptopine on Transient Outward Potassium Current in Rabbit Ventricular Myocytes

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          Abstract

          Objective: To investigate the mechanism of α-allocryptopine-induced inhibition of the transient outward potassium current ( I<sub>to</sub>) in rabbit left-ventricular myocytes. Methods: We used the whole-cell patch-clamp technique to record the I<sub>to</sub> in the myocytes, which were isolated from the rabbit left ventricle by a Langendorff-perfusion device. Results: Allocryptopine decreased the amplitude and the density of the I<sub>to</sub> in a concentration-dependent (range from 1 to 100 µ M with an IC<sub>50</sub> value of 37 ± 8 µ M) and frequency- or use-independent manner. At a test potential of +50 mV, the peak current density of I<sub>to</sub> was decreased from 21.56 ± 3.24 to 13.37 ± 2.86 pA/pF by 30 µ M allocryptopine. The fast time constant of I<sub>to</sub> inactivation was reduced from 9.8 ± 1.8 to 5.7 ± 0.7 ms and the slow time constant of I<sub>to</sub> was reduced from 50.8 ± 9.0 to 32.2 ± 12.7 ms by 30 µ M allocryptopine. The inactivated curve slope was changed from –19.2 ± 7.1 to –7.5 ± 0.6 mV, while the half-activated voltage and activated curve slope and half-inactivated voltage values were not affected by allocryptopine. Transmural heterogeneity of the I<sub>to</sub> was decreased in the presence of allocryptopine. At a test potential of +50 mV, the densities of I<sub>to</sub> were reduced by 28.6% (epimyocardium), 50.3% (midmyocardium) and 20.1% (endocardium) after expoure to 30 µ M allocryptopine.Transmural dispersion of the I<sub>to</sub> was reduced from 11.2 ± 1.2 to 4.7 ± 0.6 pA/pF by 30 µ M allocryptopine. Conclusion: Allocryptopine produced a blocking effect on the I<sub>to</sub> in cardiac myocytes, which may be an important mechanism in its antiarrhythmic effect.

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          Most cited references 22

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          Distress and empathy: two qualitatively distinct vicarious emotions with different motivational consequences.

          The construct of empathy may be located conceptually at several different points in the network of interpersonal cognition and emotion. We discuss one specific form of emotional empathy--other-focused feelings evoked by perceiving another person in need. First, evidence is reviewed suggesting that there are at least two distinct types of congruent emotional responses to perceiving another in need: feelings of personal distress (e.g., alarmed, upset, worried, disturbed, distressed, troubled, etc.) and feelings of empathy (e.g., sympathetic, moved, compassionate, tender, warm, softhearted, etc.). Next, evidence is reviewed suggesting that these two emotional responses have different motivational consequences. Personal distress seems to evoke egoistic motivation to reduce one's own aversive arousal, as a traditional Hullian tension-reduction model would propose. Empathy does not. The motivation evoked by empathy may instead be altruistic, for the ultimate goal seems to be reduction of the other's need, not reduction of one's own aversive arousal. Overall, the recent empirical evidence appears to support the more differentiated view of emotion and motivation proposed long ago by McDougall, not the unitary view proposed by Hull and his followers.
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            Toward a neurobiology of obsessive-compulsive disorder.

             A Graybiel,  S. Rauch (2000)
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              Feeling, caring, knowing: different types of empathy deficit in boys with psychopathic tendencies and autism spectrum disorder

              Background Empathy dysfunction is one of the hallmarks of psychopathy, but it is also sometimes thought to characterise autism spectrum disorders (ASD). Individuals with either condition can appear uncaring towards others. This study set out to compare and contrast directly boys with psychopathic tendencies and boys with ASD on tasks assessing aspects of affective empathy and cognitive perspective taking. The main aim of the study was to assess whether a distinct profile of empathy deficits would emerge for boys with psychopathic tendencies and ASD, and whether empathy deficits would be associated with conduct problems in general, rather than psychopathic tendencies or ASD specifically. Methods Four groups of boys aged between 9 and 16 years (N = 96) were compared: 1) psychopathic tendencies, 2) ASD, 3) conduct problems and 4) comparison. Tasks were included to probe attribution of emotions to self, empathy for victims of aggression and cognitive perspective-taking ability. Results Boys with psychopathic tendencies had a profile consistent with dysfunctional affective empathy. They reported experiencing less fear and less empathy for victims of aggression than comparison boys. Their cognitive perspective-taking abilities were not statistically significantly different from those of comparison boys. In contrast, boys with ASD had difficulties with tasks requiring cognitive perspective taking, but reported emotional experiences and victim empathy that were in line with comparison boys. Boys with conduct problems did not differ from comparison boys, suggesting that the affective empathy deficit seen in boys with psychopathic tendencies was specific to that group, rather than common to all boys with conduct problems. Conclusions Although both groups can appear uncaring, our findings suggest that the affective/information processing correlates of psychopathic tendencies and ASD are quite different. Psychopathic tendencies are associated with difficulties in resonating with other people’s distress, whereas ASD is characterised by difficulties in knowing what other people think.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2008
                October 2008
                23 April 2008
                : 111
                : 4
                : 229-236
                Affiliations
                aElectrophysiology of Laboratory, bMolecular Laboratory, and cPathophysiology of Laboratory, Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China
                Article
                127443 Cardiology 2008;111:229–236
                10.1159/000127443
                18434730
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 6, References: 27, Pages: 8
                Categories
                Original Research

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