| External site for local anesthetic block of cardiac Na+ channels. | |
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MedLine Citation:
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PMID: 1645415 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report patch clamp studies of single Na+ channels from cardiac ventricular and Purkinje cells that support the hypothesis that local anesthetics can act from the outside of the membrane, and that demonstrate some aspects of their mechanism of action. Inclusion of lidocaine (0.1 mM) or QX-314 (0.5 mM), a membrane-impermeant, quaternary ammonium derivative of lidocaine, in the pipette solution for on-cell single channel recording demonstrated four important findings. (1) The open probability of the channel is reduced by drug in a use-dependent way. (2) Late openings are preferentially reduced. (3) Mean open time is shortened. (4) Hyperpolarization enhances recovery of the drug-bound channels. These findings are consistent with a hyperpolarizing shift of the transition rates for drug-bound channel. Further, we postulate that there is a drug-bound channel conformation which conducts current. At least some of the properties of local anesthetic interaction with the cardiac Na+ channels may be the result of kinetic effects mediated by binding to an external site. |
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Authors:
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C M Baumgarten; J C Makielski; H A Fozzard |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 23 Suppl 1 ISSN: 0022-2828 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 1991 Feb |
Date Detail:
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Created Date: 1991-07-03 Completed Date: 1991-07-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 85-93 Citation Subset: IM |
Affiliation:
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Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0551. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Local
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pharmacology* Animals Dogs Lidocaine / analogs & derivatives*, pharmacology* Membrane Potentials Myocardium / metabolism* Sodium Channels / drug effects, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL-01572/HL/NHLBI NIH HHS; HL-20592/HL/NHLBI NIH HHS; HL-24847/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Local; 0/Sodium Channels; 137-58-6/Lidocaine; 21306-56-9/QX-314 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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