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Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.
Abstract: 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.
Publication Date: 2002-06-14 PubMed ID: 12063283DOI: 10.1152/ajpheart.00622.2001Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
- Animal Health
- Animal Studies
- Cardiac Arrhythmias
- Cardiovascular Health
- Clinical Study
- Comparative Study
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Genes
- Heart
- Horses
- Immunoblotting
- Immunostaining
- In Vivo
- Laboratory Methods
- Molecular biology
- Physiology
- Potassium
- Protein
- Real-Time PCR
- Species Comparison
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study investigates the involvement of certain potassium channel proteins (ERG1, KCNQ1, and KCNE1) in the heart functions of horses, and their potential connection to heart irregularities, focusing on long QT syndrome (LQTS). It adds to a body of work suggesting these proteins play a similar role in horses as in other species such as humans and dogs.
Purpose and Methods
- The researchers aimed to understand the role of three potassium channel proteins (ERG1, KCNQ1, and KCNE1) in the heart function of horses. This was in light of existing knowledge that these proteins are involved in the normal and abnormal repolarization processes related to LQTS in humans and dogs. Repolarization refers to the return of the cell to resting state after an electrical discharge.
- To examine this, the researchers used a range of scientific techniques including immunoblotting, immunostaining, and RT-PCR, to identify and study these proteins and their interaction in horse heart tissue.
Findings and Implications
- The study detected the presence of all three proteins (ERG1, KCNQ1, KCNE1) in horse heart tissue. Furthermore, it found that ERG1 and KCNQ1 demonstrated interaction with KCNE1, suggesting they function together in the heart’s electrical activity.
- The research also found that both ERG1 and KCNQ1 proteins are sensitive to Peptide N-glycosidase F, pointing to the glycoprotein nature of these channels.
- The treatment of heart samples with antagonists (molecules that inhibit the functions of specific proteins), resulted in prolonged cardiac action potential durations — this refers to the time it takes for a heart cell to ‘reset’ its electrical state after a heartbeat. This implies that these proteins play a crucial role in determining this aspect of heart function.
- These findings suggest that horses, like humans and dogs, may be susceptible to LQTS, a condition characterized by an abnormal heart rhythm that can lead to fainting, seizures, or sudden death.
- Overall, these results suggest that the repolarizing currents in horse hearts function similarly to those in humans and dogs. Future research could extend to exploring potential treatments for arrhythmias in horses, or use horse models to study human arrhythmias.
Cite This Article
APA
Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF, Freeman LC.
(2002).
Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.
Am J Physiol Heart Circ Physiol, 283(1), H126-H138.
https://doi.org/10.1152/ajpheart.00622.2001 Publication
Researcher Affiliations
- Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802, USA.
MeSH Terms
- Action Potentials / drug effects
- Action Potentials / physiology
- Animals
- Anti-Arrhythmia Agents / pharmacology
- Benzopyrans / pharmacology
- Cell Line
- Cisapride / pharmacology
- Cricetinae
- ERG1 Potassium Channel
- Ether-A-Go-Go Potassium Channels
- Horses
- Humans
- Immunoblotting
- Immunohistochemistry
- In Vitro Techniques
- KCNQ Potassium Channels
- KCNQ1 Potassium Channel
- Long QT Syndrome / etiology
- Myocardium / cytology
- Myocardium / metabolism
- Patch-Clamp Techniques
- Piperidines / pharmacology
- Potassium / metabolism
- Potassium Channel Blockers
- Potassium Channels / biosynthesis
- Potassium Channels / genetics
- Potassium Channels / metabolism
- Potassium Channels, Voltage-Gated
- Protein Binding / physiology
- RNA, Messenger / metabolism
- Swine
Grant Funding
- HD-36002 / NICHD NIH HHS
Citations
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