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Am J Physiol Heart Circ Physiol (March 14, 2002). doi:10.1152/ajpheart.00622.2001
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Articles in PresS, published online ahead of print March 14, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00622.2001
Submitted on July 18, 2001
Accepted on March 4, 2002

Expression and co-association of ERG1, KCNQ1 and KCNE1 potassium channel proteins in horse heart

Melissa R. Finley1, Yan Li1, Fei Hua2, James Lillich1, Kathy E. Mitchell1, Suhasini Ganta1, Robert F. Gilmour, Jr.2, and Lisa C. Freeman1*

1 Anatomy & Physiology, Kansas State University, Manhattan, KS, USA
2 Biomedical Sciences, Cornell University, Ithaca, NY, USA

* To whom correspondence should be addressed. E-mail: freeman{at}vet.ksu.edu.

In dog and man, potassium channels formed by ERG1 (KCNH2) and KCNQ1 {alpha}-subunits, in association with KCNE ß-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. PNGase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 co-immunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (293B). Patch clamp confirmed the presence of IKs. 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 co-association between ERG1 and KCNE1 in cardiac tissue.




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