Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:396 |
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| Enthalten in: |
Naunyn-Schmiedeberg's archives of pharmacology - 396(2023), 12 vom: 10. Dez., Seite 3775-3788 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Teixeira-Fonseca, Jorge Lucas [VerfasserIn] |
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| Links: |
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| Themen: |
1HQ3YCN4GS |
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| Anmerkungen: |
Date Completed 16.11.2023 Date Revised 23.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00210-023-02569-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Teixeira-Fonseca, Jorge Lucas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension |
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| 520 | |a © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Arrhythmia | |
| 650 | 4 | |a ML365 | |
| 650 | 4 | |a Monocrotaline | |
| 650 | 4 | |a Pulmonary hypertension | |
| 650 | 4 | |a Right atrium | |
| 650 | 4 | |a TASK-1 | |
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| 700 | 1 | |a Joviano-Santos, Julliane V |e verfasserin |4 aut | |
| 700 | 1 | |a Beserra, Samuel Santos |e verfasserin |4 aut | |
| 700 | 1 | |a de Lima Conceição, Michael Ramon |e verfasserin |4 aut | |
| 700 | 1 | |a Leal-Silva, Polyana |e verfasserin |4 aut | |
| 700 | 1 | |a Marques, Leisiane Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a Souza, Diego Santos |e verfasserin |4 aut | |
| 700 | 1 | |a Roman-Campos, Danilo |e verfasserin |4 aut | |
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