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.
Authors: Pedersen Philip Juul, Thomsen Kirsten Brolin, Olander Emma Rie, Hauser Frank, Tejada Maria de los Angeles, Poulsen Kristian Lundgaard, Grubb Soren, Buhl Rikke, Calloe Kirstine, Klaerke Dan Arne
Journal: PloS one
Summary
# Editorial Summary: Equine Cardiac Potassium Channels and Sudden Death Risk Sudden cardiac death remains an unexplained problem in equine practice, yet the underlying electrophysiological mechanisms have received limited investigation. Researchers isolated and characterised the equine KCNH2 gene and its regulatory KCNE2 subunit, which together encode the KV11.1 potassium channel critical for cardiac repolarisation, then compared their molecular properties and drug sensitivity to human equivalents using oocyte expression systems and isolated equine ventricular tissue. The equine KV11.1 channel displayed notably larger currents than its human counterpart, with faster activation at lower voltages and slower inactivation kinetics—differences that may predispose horses to arrhythmias, particularly at lower heart rates. When exposed to terfenadine (a common antihistamine), equine KV11.1 channels were susceptible to pharmacological blockade, resulting in prolonged action potential duration in ventricular tissue, mirroring the acquired Long QT syndrome seen in humans receiving QT-prolonging drugs. These findings suggest that equine myocardium may be inherently vulnerable to both congenital ion-channel mutations and acquired disturbances from medication, warranting careful consideration of drug interactions and screening protocols in horses with suspected arrhythmias or unexplained sudden death events.
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Practical Takeaways
- •Horses appear genetically susceptible to QT prolongation and sudden cardiac death similar to humans, warranting cardiac screening in at-risk populations
- •Certain medications (like terfenadine) may pose cardiac safety risks in horses by blocking KV11.1 channels; veterinarians should review drug safety profiles for cardiac effects
- •Understanding equine cardiac electrophysiology may help explain some cases of sudden, unexplained deaths in horses and guide preventive management strategies
Key Findings
- •Equine KV11.1 channel shares 93% homology with human homolog and exhibits larger currents with slower inactivation kinetics
- •Equine KV11.1 is susceptible to pharmacological block by terfenadine, which prolongs action potential duration particularly at slow pacing rates
- •Structural and functional differences between equine and human KV11.1 suggest horses may be predisposed to both congenital and acquired Long QT syndrome