| Nimodipine block of calcium channels in rat vascular smooth muscle cell lines. Exceptionally high-affinity binding in A7r5 and A10 cells. | |
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MedLine Citation:
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PMID: 2559139 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcium channel currents were studied in the A10 and A7r5 cell lines derived from rat thoracic aorta muscle cells. The whole-cell variation of the patch voltage clamp technique was used. Results with each cell line were nearly identical. Two types of Ca channels were found in each cell line that are similar to the L-type and T-type Ca channels found in excitable cells. Nimodipine block of the L-type Ca channels in both cell lines is more potent than in previously studied tissues. The kinetics of nimodipine block are accounted for by a model that postulates 1:1 drug binding to open Ca channels with an apparent dissociation constant (KO) of 16-45 pM. In A7r5 cells, the rate of onset of nimodipine block increases with the test potential, in quantitative agreement with the model of open channel block. The apparent association rate (f) is 1.4 x 10(9) M-1 s-1; the dissociation rate (b) is about 0.024 s-1. In anterior pituitary cells (GH4C1 cells), KO is 30 times larger; b is only twice as fast, but f is 15 times slower. The comparative kinetic analysis indicates that the high-affinity binding site for nimodipine is similar in both GH4C1 and A7r5 cells, but nimodipine diffuses much faster or has a larger partition coefficient into the plasmalemma of A7r5 cells than for GH4C1 cells. Unusually high-affinity binding was not observed in earlier 45Ca flux studies with A10 and A7r5 cells. The model of open channel block accounts for the discrepancy; only a small fraction of the Ca channels are in the high affinity open state under the conditions used in 45Ca flux studies, so an effective binding constant is measured that is much greater than the dissociation constant for high-affinity binding. |
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Authors:
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R T McCarthy; C J Cohen |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: The Journal of general physiology Volume: 94 ISSN: 0022-1295 ISO Abbreviation: J. Gen. Physiol. Publication Date: 1989 Oct |
Date Detail:
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Created Date: 1990-02-27 Completed Date: 1990-02-27 Revised Date: 2008-11-20 |
Medline Journal Info:
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Nlm Unique ID: 2985110R Medline TA: J Gen Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 669-92 Citation Subset: IM |
Affiliation:
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Miles Institute for Preclinical Pharmacology, West Haven, Connecticut 06516. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Calcium Channels / drug effects*, metabolism Cell Line Kinetics Models, Biological Muscle, Smooth, Vascular / drug effects*, metabolism Nimodipine / metabolism, pharmacology* Rats |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels; 66085-59-4/Nimodipine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
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Journal Information Journal ID (nlm-ta): J Gen Physiol ISSN: 0022-1295 ISSN: 1540-7748 Publisher: The Rockefeller University Press |
Article Information Download PDF  Print publication date: Day: 1 Month: 10 Year: 1989 Volume: 94 Issue: 4 First Page: 669 Last Page: 692 ID: 2228965 Publisher Id: 90132494 PubMed Id: 2559139 |
| Nimodipine block of calcium channels in rat vascular smooth muscle cell lines. Exceptionally high-affinity binding in A7r5 and A10 cells | |
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