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PloS one2015; 10(9); e0138320; doi: 10.1371/journal.pone.0138320

Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether à Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium.

Abstract: The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death--conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two-electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2±1.1 mV and -17.3±0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS.
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Publication Date: 2015-09-16 PubMed ID: 26376488PubMed Central: PMC4574097DOI: 10.1371/journal.pone.0138320Google Scholar: Lookup
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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 research examines the genes KCNH2 and KCNE2 in horses, which are responsible for the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. The study explores the association this channel has with the risk of sudden cardiac death in horses, and the findings suggest that horses could be susceptible to both congenital and acquired Long QT syndrome, similar to humans.

Genes Studied and Their Function

  • The researchers focused on the KCNH2 and KCNE2 genes in horses. These genes code for the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2, respectively.
  • These channels play a critical role in the repolarization of the cardiac action potential. In humans, any mutation or drug therapy that affects the KV11.1 channel triggers a prolongation of the QT intervals on the ECG, leading to an increased risk of ventricular tachyarrhythmia and sudden cardiac death. These conditions are known as congenital or acquired Long QT syndrome (LQTS).

Research Methodology

  • The researchers sequenced the cDNA of the KCNH2 and KCNE2 genes using techniques like RACE and conventional PCR on mRNA, extracted from the myocardial tissue of horses.
  • The equine KV11.1 and KCNE2 cDNA showed a high resemblance to human genes (93 and 88%, respectively).
  • The equine and human KV11.1 and KV11.1/KCNE2 were subsequently expressed in Xenopus laevis oocytes to be studied via the two-electrode voltage-clamp.

Findings and Conclusion

  • The study found that the currents generated by equine KV11.1 were larger compared to the human KV11.1. Moreover, the voltage dependence of activation shifted to more negative values for the equine KV11.1.
  • The slow onset of inactivation in the equine KV11.1 as compared to the human equivalent could explain the larger amplitude of the equine current.
  • The equine KV11.1 channel was found to be susceptible to pharmacological block with terfenadine.
  • The importance of KV11.1 was further investigated in equine right ventricular wedge preparations. Here, terfenadine was found to prolong action potential duration with the most pronounced effect at slow pacing.
  • All these findings indicate that horses could be predisposed to both congenital and acquired LQTS, similar to humans.

Cite This Article

APA
Pedersen PJ, Thomsen KB, Olander ER, Hauser F, Tejada Mde L, Poulsen KL, Grubb S, Buhl R, Calloe K, Klaerke DA. (2015). Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether à Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium. PLoS One, 10(9), e0138320. https://doi.org/10.1371/journal.pone.0138320

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 9
Pages: e0138320
PII: e0138320

Researcher Affiliations

Pedersen, Philip Juul
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Thomsen, Kirsten Brolin
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Olander, Emma Rie
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Hauser, Frank
  • Center for Functional and Comparative Insect Genomics, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Tejada, Maria de los Angeles
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Poulsen, Kristian Lundgaard
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Grubb, Soren
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Buhl, Rikke
  • Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Calloe, Kirstine
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Klaerke, Dan Arne
  • Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

MeSH Terms

  • Action Potentials
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Ether-A-Go-Go Potassium Channels / genetics
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Female
  • Horses
  • Humans
  • Long QT Syndrome
  • Molecular Sequence Data
  • Mutation / genetics
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oocytes / cytology
  • Oocytes / metabolism
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • Protein Subunits
  • Sequence Homology, Amino Acid
  • Xenopus laevis

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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