دورية أكاديمية
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
| العنوان: | Molecular determinants of state-dependent block of Na+ channels by local anesthetics. |
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| المؤلفون: | Ragsdale DS; Department of Pharmacology, University of Washington, Seattle 98195., McPhee JC, Scheuer T, Catterall WA |
| المصدر: | Science (New York, N.Y.) [Science] 1994 Sep 16; Vol. 265 (5179), pp. 1724-8. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Print ISSN: 0036-8075 (Print) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Anesthetics, Local/*pharmacology , Etidocaine/*pharmacology , Sodium Channels/*drug effects, Action Potentials ; Anesthetics, Local/metabolism ; Animals ; Binding Sites ; Etidocaine/metabolism ; Lidocaine/analogs & derivatives ; Lidocaine/metabolism ; Lidocaine/pharmacology ; Mutagenesis, Site-Directed ; Oocytes ; Rats ; Sodium Channels/chemistry ; Sodium Channels/genetics ; Sodium Channels/metabolism ; Xenopus |
| مستخلص: | Sodium ion (Na+) channels, which initiate the action potential in electrically excitable cells, are the molecular targets of local anesthetic drugs. Site-directed mutations in transmembrane segment S6 of domain IV of the Na+ channel alpha subunit from rat brain selectively modified drug binding to resting or to open and inactivated channels when expressed in Xenopus oocytes. Mutation F1764A, near the middle of this segment, decreased the affinity of open and inactivated channels to 1 percent of the wild-type value, resulting in almost complete abolition of both the use-dependence and voltage-dependence of drug block, whereas mutation N1769A increased the affinity of the resting channel 15-fold. Mutation I1760A created an access pathway for drug molecules to reach the receptor site from the extracellular side. The results define the location of the local anesthetic receptor site in the pore of the Na+ channel and identify molecular determinants of the state-dependent binding of local anesthetics. |
| معلومات مُعتمدة: | P01-HL44948 United States HL NHLBI NIH HHS; R01-NS15751 United States NS NINDS NIH HHS |
| المشرفين على المادة: | 0 (Anesthetics, Local) 0 (Sodium Channels) 21306-56-9 (QX-314) 98PI200987 (Lidocaine) I6CQM0F31V (Etidocaine) |
| تواريخ الأحداث: | Date Created: 19940916 Date Completed: 19941012 Latest Revision: 20190618 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1126/science.8085162 |
| PMID: | 8085162 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0036-8075 |
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| DOI: | 10.1126/science.8085162 |