| Evidence for aconitine-induced inhibition of delayed rectifier K(+) current in Jurkat T-lymphocytes. | |
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MedLine Citation:
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PMID: 21782880 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aconitine (ACO) is a highly toxic diterpenoid alkaloid and known to exert the immunomodulatory action. However, whether it has any effects on ion currents in immune cells remains unknown. The effects of ACO and other related compounds on ion currents in Jurkat T-lymphocytes were investigated in this study. ACO suppressed the amplitude of delayed-rectifier K(+) current (I(K(DR))) in a time- and concentration-dependent manner. Margatoxin (100nM), a specific blocker of K(V)1.3-encoded current, decreased the I(K(DR)) amplitude in these cells and the ACO-induced inhibition of I(K(DR)) was not reversed by 1-ethyl-2-benzimidazolinone (30μM) or nicotine (10μM). The IC(50) value for ACO-mediated inhibition of I(K(DR)) was 5.6μM. ACO accelerated the inactivation of I(K(DR)) with no change in the activation rate of this current. Increasing the ACO concentration not only reduced the I(K(DR)) amplitude, but also accelerated the inactivation time course of the current. With the aid of minimal binding scheme, the inhibitory action of ACO on I(K(DR)) was estimated with a dissociation constant of 6.8μM. ACO also shifted the inactivation curve of I(K(DR)) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for I(K(DR)) was enhanced in the presence of ACO. In Jurkat cells incubated with amiloride (30μM), the ACO-induced inhibition of I(K(DR)) remained unaltered. In RAW 264.7 murine macrophages, ACO did not modify the kinetics of I(K(DR)), although it suppressed I(K(DR)) amplitude. Taken together, these effects can significantly contribute to its action on functional activity of immune cells if similar results are found in vivo. |
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Authors:
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Sheng-Nan Wu; Bing-Shuo Chen; Yi-Ching Lo |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-18 |
Journal Detail:
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Title: Toxicology Volume: - ISSN: 1879-3185 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ireland Ltd. |
Affiliation:
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Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan; Department of Anatomy and Cell Biology, National Cheng Kung University Medical College, Tainan City, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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