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
| Autor: | Philip J. Pedersen, Dan A. Klaerke, Kristian L. Poulsen, Maria de los Angeles Tejada, Emma Rie Olander, Kirstine Calloe, Frank Hauser, Kirsten B. Thomsen, Søren Grubb, Rikke Buhl |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Protein subunit Long QT syndrome Molecular Sequence Data Xenopus lcsh:Medicine Action Potentials Xenopus laevis Complementary DNA Internal medicine medicine Repolarization Animals Humans Terfenadine Amino Acid Sequence Horses Cloning Molecular lcsh:Science Multidisciplinary biology Sequence Homology Amino Acid Myocardium lcsh:R KCNE2 Cardiac action potential medicine.disease biology.organism_classification Ether-A-Go-Go Potassium Channels Long QT Syndrome Protein Subunits Endocrinology Potassium Channels Voltage-Gated Mutation biology.protein Oocytes lcsh:Q Female medicine.drug Research Article |
| Zdroj: | Pedersen, P J, Thomsen, K B, Olander, E R, Hauser, F, Tejada, M D L A, Poulsen, K L, Grubb, S J, Buhl, R, Callø, K & Klærke, D A 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, vol. 10, no. 9, e0138320 . https://doi.org/10.1371/journal.pone.0138320 PLoS ONE PLoS ONE, Vol 10, Iss 9, p e0138320 (2015) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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