Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.
In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.
Finley
Melissa R
MR
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802, USA.
Li
Yan
Y
Hua
Fei
F
Lillich
James
J
Mitchell
Kathy E
KE
Ganta
Suhasini
S
Gilmour
Robert F
RF
Freeman
Lisa C
LC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D020117:Cisapride / Q000494:pharmacology; D006224:Cricetinae; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006736:Horses; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000209:etiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C418492:KCNE3 protein, human; C000606913:KCNH2 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; C059983:potassium channel protein I(sk); C087257:L 706000; D011188:Potassium; D020117:Cisapride