Linked Life Data

7586228

Source:http://linkedlifedata.com/resource/pubmed/id/7586228

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-12-26
pubmed:abstractText
Methanesulfonanilide derivatives such as dofetilide are members of the widely used Class III group of cardiac antiarrhythmic drugs. A methanesulfonanilide-sensitive cardiac current has been identified as IKr, the rapidly activating component of the repolarizing outward cardiac K+ current, IK. IKr may be encoded by the human ether-related gene (hERG), which belongs to the family of voltage-dependent K+ (Kv) channels having six putative transmembrane segments. The hERG also expresses an inwardly rectifying, methanesulfonanilide-sensitive K+ current. Here we show that hIRK, a member of the two-transmembrane-segment family of inward K+ rectifiers that we have cloned from human heart, is a target for dofetilide. hIRK currents, expressed heterologously in Xenopus oocytes, are blocked by dofetilide at submicromolar concentrations (IC50 = 533 nmol/L at 40 mV and 20 degrees C). The drug has no significant blocking effect on the human cardiac Kv channels hKv1.2, hKv1.4, hKv1.5, or hKv2.1. The block is voltage dependent, use dependent, and shortens open times in a manner consistent with open-channel block. While steady state block is strongest at depolarized potentials, recovery from block is very slow even at hyperpolarized potentials (tau = 1.17 seconds at -80 mV). Thus, block of hIRK may persist during diastole and might thereby affect cardiac excitability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0009-7330
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1151-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Cloned human inward rectifier K+ channel as a target for class III methanesulfonanilides.
pubmed:affiliation
Rammelkamp Center for Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't