Stretch-activated two-pore-domain (K2P) potassium channels in the heart: Focus on atrial fibrillation and heart failure
| Autor: | Dierk Thomas, Antonius Ratte, Stefan Kallenberger, Gábor Veres, Arjang Ruhparwar, Joachim R. Ehrlich, Ursula Tochtermann, Jan S. Schulte, Maria-Patapia Zafeiriou, Niels Voigt, Constanze Schmidt, Matthias Karck, Felix Wiedmann, Beatrix Scholz, Frank U. Müller, Hugo A. Katus |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Messenger RNA medicine.medical_specialty Heart disease Chemistry Transgene Biophysics Atrial fibrillation 030204 cardiovascular system & hematology medicine.disease Potassium channel 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Downregulation and upregulation Heart failure Internal medicine medicine Mechanosensitive channels Molecular Biology |
| Zdroj: | Progress in Biophysics and Molecular Biology. 130:233-243 |
| ISSN: | 0079-6107 |
| DOI: | 10.1016/j.pbiomolbio.2017.05.004 |
| Popis: | Two-pore-domain potassium (K 2P ) channels modulate cellular excitability. The significance of stretch-activated cardiac K 2P channels (K 2P 2.1, TREK-1, KCNK 2; K 2P 4.1, TRAAK, KCNK 4; K 2P 10.1, TREK-2, KCNK 10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K 2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K 2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery. In addition, control mice and mouse models of AF (cAMP-response element modulator (CREM)-IbΔC-X transgenic animals) or HF (cardiac dysfunction induced by transverse aortic constriction, TAC) were employed. Human and murine KCNK 2 displayed highest mRNA abundance among mechanosensitive members of the K 2P channel family (V > A). Disease-associated K 2P 2.1 remodeling was studied in detail. In patients with impaired left ventricular function, atrial KCNK 2 (K 2P 2.1) mRNA and protein expression was significantly reduced. In AF subjects, downregulation of atrial and ventricular KCNK 2 (K 2P 2.1) mRNA and protein levels was observed. AF-associated suppression of atrial Kcnk 2 (K 2P 2.1) mRNA and protein was recapitulated in CREM-transgenic mice. Ventricular Kcnk 2 expression was not significantly altered in mouse models of disease. In conclusion, mechanosensitive K 2P 2.1 and K 2P 10.1 K + channels are expressed throughout the heart. HF- and AF-associated downregulation of KCNK 2 (K 2P 2.1) mRNA and protein levels suggest a mechanistic contribution to cardiac arrhythmogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect