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- W2047862010 abstract "Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT interval in the ECG. Human and canine patients are predisposed to syncopal episodes and sudden cardiac death (SCD). In humans mutations in 13 genes affecting ion channel function are involved in LQTS. KCNQ1 and KCNH2 represent the molecular correlate of the slow (Iks) and fast (Ikr) repolarizing K+ currents in the heart and mutations in these genes are responsible for about 90% of cases. Sudden death is well known in horses and unacceptable from an ethical, financial and safety point of view. Up to 68% of sudden deaths in racehorses occur of unknown reasons, but are often suspected to be exercise-induced acute cardiovascular failure. The objective of this project is to clone and characterize the equine KCNH2 and KCNQ1 channels. This may allow for the diagnosing of possible LQTS syndromes in horses.To clone the channels and their regulatory subunits mRNA was isolated from equine ventricular myocytes and full length PCR products for KCNH2, KCNQ1, KCNE1 and KCNE2 were amplified using RACE PCR. The products were sequenced and subcloned for expression in Xenopus oocytes. After expression two-electrode voltage clamp was performed to characterize the electrophysiological properties of the channels.The protein sequences for the equine channels and beta-subunits were compared with the respective human sequences and showed the following homologies, KCNH2: 99%, KCNQ: 91%, KCNE1: 80% and KCNE2: 90%. After expression in Xenopus oocytes, the equine KCNH2 showed electrophysiological properties resembling the human channel. The equine KCNQ1/KCNE channels await thorough electrophysiological characterization.In conclusion, it is expected that the KCNH2 and KCNQ are responsible for repolarization of the equine heart and mutations in these proteins may lead to yet unknown equine LQTS." @default.
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- W2047862010 date "2014-01-01" @default.
- W2047862010 modified "2023-09-28" @default.
- W2047862010 title "Cloning of Equine KCNH2 and KCNQ1 as the Basis for Diagnosing Long QT Syndrome in Horses" @default.
- W2047862010 doi "https://doi.org/10.1016/j.bpj.2013.11.3073" @default.
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