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Effects of chronic heart failure on the electrophysiological properties of the peripheral chemoreceptor cells from rats

Grant number: 22/14681-9
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2023
Field of knowledge:Biological Sciences - Biophysics - Cellular Biophysics
Principal Investigator:Davi José de Almeida Moraes
Grantee:Sara Lima Raduan Scarpari
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:21/06886-7 - Role of purinergic receptors in the carotid body in heart failure, AP.JP2

Abstract

The carotid body (CB) is a peripheral chemoreceptor located in the carotid artery bifurcation, presenting two types of cells: type I (glomus cells) and type II. Glomus cells can detect changes in O2 partial pressure in arterial blood, being organized close to the blood vessels originating from the carotid artery, while type II cells are organized around them, promoting support, and participating in the sensory process of CB. Heart failure (HF) affects thousands of people, with functional consequences such as partial loss of cardiac output, sympathetic hyperactivity, shortness of breath, and bronchoconstriction, interfering directly with the patient's quality of life, which can lead to death. Recent studies demonstrated that removing CB reduced sympathetic activity, improving respiratory instability and arrhythmia in animals and humans. In this sense, studying the cells that compose the CB and their electrophysiological properties and dysfunctions in animal models with HF will reveal important cellular information to understand better the genesis of bronchoconstriction and sympathetic hyperactivity in patients with this pathology. Herein, we hypothesized that HF increases the excitability and sensitivity to O2 of the CB cells from rats. We will use 7-week-old Wistar Hannover rats that undergo HF induction surgery employing left coronary artery ligation or undergo sham surgery. The CB will be extracted four weeks later and sliced (150 ¼m). The electrical properties (capacitance, resting membrane potential, input resistance, and membrane conductance) of CB cells will be recorded using the whole cell patch clamp technique in current clamp and voltage clamp configurations under normoxic (21% O2) and hypoxic (10% O2) conditions. The results to be obtained will reveal the cellular mechanisms by which HF increases the activity of CB, contributing to bronchoconstriction and sympathetic hyperactivity in this pathology.

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