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PMID: 2446150 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Lidocaine blocks open and inactivated cardiac sodium channels.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 336 ·No. 2 ·1987-08-00 ·Pages 224-31

Matsubara T, Clarkson C, Hondeghem L

Abstract

Guinea-pig papillary muscles were voltage-clamped using the single sucrose gap technique. The maximum upstroke velocity of the action potential (Vmax) was used as an indicator of the sodium conductance. Lidocaine (5 mumol/l to 40 mumol/l) reduced Vmax in a use-dependent fashion. Block of sodium channels developed during channel opening and while the channels were inactivated. Block of inactivated channels was not voltage-dependent over the -40 mV to +40 mV range. Recovery from block occurs upon repolarization, and for a given diastolic interval the recovery is more complete as the membrane potential is hyperpolarized over the -80 mV to -150 mV range. These results can be accounted for in terms of the modulated receptor hypothesis, where lidocaine has a low affinity for rested sodium channels, but a high affinity for open and inactivated channels.

MeSH Terms
Action Potentials/drug effects Animals Guinea Pigs Heart/drug effects In Vitro Techniques Ion Channels/drug effects Lidocaine/pharmacology Membrane Potentials/drug effects Models, Cardiovascular Sodium/metabolism
Chemicals
Ion Channels Lidocaine Sodium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Matsubara T
Department of Pharmacology, University of California, San Francisco 94143.
Clarkson C
Hondeghem L
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30 references, click to expand
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00165809
Published
1987-08-00
Pages
224-31
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00165809 View journal details
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