Abstract:
:Block of Ca2+ currents by the dihydropyridine drug nitrendipine was studied in single canine ventricular cells by using the whole-cell variant of the patch clamp technique. When cells were held at depolarized membrane potentials at which Ca2+ currents were approximately equal to 70% inactivated, nitrendipine blocked Ca2+ currents very potently, with half-block by subnanomolar concentrations. The concentration dependence of block had the form expected for 1:1 binding, with an apparent dissociation constant (Kd) of 0.36 nM. In contrast, when cells were held at hyperpolarized potentials, nitrendipine blocked Ca2+ currents much less potently (Kd approximately equal to 700 nM). The results can be explained if nitrendipine binds very tightly to the inactivated state of the Ca2+ channel and only weakly to the normal resting state. The Kd estimated for binding to the inactivated state is very similar to the dissociation constants previously found for high-affinity [3H]nitrendipine binding to membrane fragments from heart, smooth muscle, brain, and other tissues; moreover, the concentration-dependent kinetics of binding to the inactivated state are similar to those reported for [3H]nitrendipine binding to membranes. These results make it seem very likely that the high-affinity [3H]nitrendipine binding site is an inactivated state of the Ca2+ channel.
journal_name
Proc Natl Acad Sci U S Aauthors
Bean BPdoi
10.1073/pnas.81.20.6388subject
Has Abstractpub_date
1984-10-01 00:00:00pages
6388-92issue
20eissn
0027-8424issn
1091-6490journal_volume
81pub_type
杂志文章abstract::The high susceptibility of human immunoglobulin D to proteolytic degradation affects its biological function, metabolism, and immunoassay. High-pressure liquid chromatography was used to investigate the mechanism and rate of limited proteolytic cleavage of IgD and also to identify, isolate, and quantify the reaction p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.84.1.61
更新日期:1987-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.85.21.8350
更新日期:1988-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1972-03-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1990-02-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1974-10-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-05-28 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2001-10-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.84.14.4856
更新日期:1987-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1986-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1975-03-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1992-12-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.93.14.6869
更新日期:1996-07-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-02-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.88.4.1172
更新日期:1991-02-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2005-02-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.86.18.7113
更新日期:1989-09-01 00:00:00
abstract::Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de novo synthesis, salvag...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2019-09-17 00:00:00