title: Molecular correlates of altered expression of potassium currents in failing rabbit myocardium.
abstract: Action potential (AP) prolongation is a hallmark of failing myocardium. Functional downregulation of K currents is a prominent feature of cells isolated from failing ventricles. The detailed changes in K current expression differ depending on the species, the region of the heart, and the mechanism of induction of heart failure. We used complementary approaches to study K current downregulation in pacing tachycardia-induced heart failure in the rabbit. The AP duration (APD) at 90% repolarization was significantly longer in cells isolated from failing hearts compared with controls (539 +/- 162 failing vs. 394 +/- 114 control, P < 0.05). The major K currents in the rabbit heart, inward rectifier potassium current (I(K1)), transient outward (I(to)), and delayed rectifier current (I(K)) were functionally downregulated in cells isolated from failing ventricles. The mRNA levels of Kv4.2, Kv1.4, KChIP2, and Kir2.1 were significantly downregulated, whereas the Kv4.3, Erg, KvLQT1, and minK were unaltered in the failing ventricles compared with the control left ventricles. Significant downregulation in the long splice variant of Kv4.3, but not in the total Kv4.3, Kv4.2, and KChIP2 immunoreactive protein, was observed in cells isolated from the failing ventricle with no change in Kv1.4, KvLQT1, and in Kir2.1 immunoreactive protein levels. Multiple cellular and molecular mechanisms underlie the downregulation of K currents in the failing rabbit ventricle.
authors.affiliation: Division of Cardiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Rose
authors.forename: Antonis A
authors.initials: AA
authors.lastname: Armoundas
authors.forename: Yanli
authors.initials: Y
authors.lastname: Tian
authors.forename: Deborah
authors.initials: D
authors.lastname: DiSilvestre
authors.forename: Miroslava
authors.initials: M
authors.lastname: Burysek
authors.forename: Victoria
authors.initials: V
authors.lastname: Halperin
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology*; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051605:Kv Channel-Interacting Proteins; D051665:Kv1.4 Potassium Channel; D008297:Male; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051672:Shal Potassium Channels
chemical_list: D002135:Calcium-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C092068:Kcne1 protein, mouse; C000606915:Kcnh2 protein, mouse; C489461:Kir2.1 channel; D051605:Kv Channel-Interacting Proteins; D051665:Kv1.4 Potassium Channel; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D011188:Potassium