Linked Life Data

1331749

Source:http://linkedlifedata.com/resource/pubmed/id/1331749

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1992-12-1
pubmed:abstractText
Previous studies have shown that chronic in vivo treatment with the antiarrhythmic drug mexiletine produces an increase in sodium channel number. We examined whether chronic mexiletine treatment would similarly regulate the level of mRNA encoding the cardiac sodium channel. RNA isolated from cardiac tissue was probed with a 2.5-kilobase cRNA transcribed with T7 RNA polymerase from the clone Na 8.4, which encodes nucleotides 3361-5868 of the alpha subunit of the RIIA sodium channel subtype. Chronic mexiletine treatment produced a 3-fold increase in the level of mRNA encoding sodium channel alpha subunits. Previous studies of cultured skeletal muscle cells had suggested that chronic sodium channel blockade may mediate an increase in sodium channel mRNA by changes in cytosolic Ca2+ concentration. To address this issue, we assessed whether verapamil would also produce up-regulation of the level of mRNA encoding the sodium channel and whether the calcium ionophore A23187 would produce the opposite effect on mRNA level. Verapamil treatment increased sodium channel mRNA level up to 3-fold, whereas in vitro A23187 treatment decreased the mRNA level 5-fold. The combination of verapamil and mexiletine produced no further increase in the mRNA level, compared with that seen with the single agents, suggesting a convergent second messenger pathway for the actions of these two drugs. These data show that the level of mRNA encoding sodium channels is substantially increased during antiarrhythmic drug treatment and suggest that change in cytosolic Ca2+ concentration is the second messenger involved in the regulation of levels of mRNA encoding the alpha subunit of the cardiac sodium channel.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
570-4
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Class I and IV antiarrhythmic drugs and cytosolic calcium regulate mRNA encoding the sodium channel alpha subunit in rat cardiac muscle.
pubmed:affiliation
Department of Pharmacology, University of Washington, Seattle 98195.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't