Linked Life Data

2553294

Source:http://linkedlifedata.com/resource/pubmed/id/2553294

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-12-7
pubmed:abstractText
The effects of the optical stereoisomers of the local anesthetic RAC109 (RAC109-I and RAC109-II) on sodium current in isolated guinea pig ventricular myocytes were investigated by use of the whole-cell variation of the patch-clamp technique. RAC109-I and RAC109-II produced similar levels of tonic block, but RAC109-I produced a significantly larger use-dependent block on repetitive pulsing to potentials positive to -60 mV. Definition of the time courses of block development at -20 mV and recovery at -140 and -160 mV indicated that RAC109-I had a higher affinity for activated and inactivated channels and dissociated more slowly at hyperpolarized potentials compared with RAC109-II. Removal of fast inactivation by alpha-chymotrypsin intensified tonic block but did not reduce use-dependent block by RAC109-I; this finding suggests that channel inactivation is not necessary for use-dependent block. The guarded-receptor model was used to calculate apparent rate constants of drug binding and unbinding. According to the model, RAC109-I and RAC109-II have significantly different unbinding rate constants for channels when they exist predominantly in rested, activated, or inactivated states, as well as significantly different binding rate constants when channels are activated. However, the apparent rates of drug binding to closed (rested and inactivated) channels are not significantly different for the two isomers; this finding indicates that drug binding to closed channels is not markedly stereospecific, in contrast to unbinding. The effects of RAC109 stereoisomers on cardiac sodium channels were also qualitatively similar to those previously reported in nerve; these findings suggest that the binding sites for local anesthetics in both tissue types have a similar structural topography.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0009-7330
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1306-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Stereoselective block of cardiac sodium channels by RAC109 in single guinea pig ventricular myocytes.
pubmed:affiliation
Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA 70112.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't