Document Detail


Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes.
MedLine Citation:
PMID:  9118489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several cloned K+ channel subunits are candidates to underlie macroscopic currents in the human heart, but direct evidence bearing on their role is lacking. The Kv1.5 K+ channel subunit has been suggested to play a potential role in human cardiac ultrarapid delayed rectifier (IKur) and transient outward (Ito) currents. To evaluate the role of proteins encoded by the Kv1.5 gene, we incubated cultured human atrial myocytes for 48 hours in medium containing antisense phosphorothioate oligodeoxynucleotides directed against octodecameric segments of the Kv1.5 mRNA coding sequence, the same concentration of homologous oligodeoxynucleotides with four mismatch mutations, or vehicle (control group). Cells exposed to antisense showed a highly significant (approximately 50%) reduction in IKur whether measured by step current at the end of a 400-millisecond depolarizing pulse, tail current at -20 mV, or current sensitive to a concentration of 4-aminopyridine (50 mumol/L) that is highly selective for IKur compared with control cells or cells exposed to mismatch oligodeoxynucleotides. In contrast, Ito was not different among the three experimental groups. When cultured human ventricular myocytes were exposed to Kv1.5 antisense oligodeoxynucleotides with the same controls, no changes occurred in either Ito or the sustained current at the end of a depolarizing pulse. We conclude that Kv1.5 channel subunits are essential to the expression of IKur and do not play a role in Ito in cultured human atrial myocytes. These studies provide the first direct evidence with an antisense approach for the equivalence between a macroscopic cardiac K+ current and a cloned K+ channel subunit and offer insights into the molecular electrophysiology of the human heart.
Authors:
J Feng; B Wible; G R Li; Z Wang; S Nattel
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation research     Volume:  80     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-04-24     Completed Date:  1997-04-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  572-9     Citation Subset:  IM    
Affiliation:
Department of Medicine and Research Center, Montreal Heart Institute, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cell Size
Cells, Cultured
Delayed Rectifier Potassium Channels
Heart Atria / drug effects,  metabolism*
Heart Ventricles / drug effects
Humans
Middle Aged
Muscle Fibers, Skeletal / drug effects,  metabolism*
Oligonucleotides, Antisense / pharmacology*
Patch-Clamp Techniques
Potassium Channels / drug effects,  metabolism*
Potassium Channels, Voltage-Gated*
Ventricular Function
Chemical
Reg. No./Substance:
0/Delayed Rectifier Potassium Channels; 0/Oligonucleotides, Antisense; 0/Potassium Channels; 0/Potassium Channels, Voltage-Gated

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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