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

Author(s)

Teixeira-Fonseca, Jorge Lucas ; Joviano-Santos, Julliane V. ; Beserra, Samuel Santos ; Conceicao, Michael Ramon de Lima ; Leal-Silva, Polyana ; Marques, Leisiane Pereira ; Souza, Diego Santos ; Roman-Campos, Danilo

• Document type: Journal article
• Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. N/A, p. 14-pg., 2023-06-20.

Abstract

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. (AU)

• FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
• Grantee: Danilo Roman Campos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/18918-0 - Role of nitric oxide in cardiac arrhythmias during Hypothyroidism
• Grantee: Diego Santos de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/15122-0 - CARDIOTOXICITY INDUCED BY THE PESTICIDE TEBUCONAZOLE IN MICE: FROM CONCEPTION TO ADULT LIFE
• Grantee: Leisiane Pereira Marques
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/14635-1 - Modeling of monogenic diseases for physiopathological studies and pharmacological tests using specialized cells derived from iPSCs
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/05584-7 - Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil
• Grantee: Danilo Roman Campos
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2