Participation of calcium-activated potassium channels in respiratory, autonomic and behavioral responses to CO2/pH and in the chemosensitivity of LC neurons

• Grant number: 21/13618-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2022
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luciane Helena Gargaglioni Batalhão
• Grantee: Luis Gustavo Alexandre Patrone
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated research grant: 20/01702-2 - Physiopathology of CO2 sensitivity: role of locus coeruleus, AP.TEM
• Associated scholarship(s): 24/22051-0 - Transcriptomic insights into the Locus coeruleus: BK channels, CO2 sensitivity, and their implications in panic disorder and respiration., BE.EP.PD

Abstract

Multiple factors are involved in the chemosensitivity process of LC neurons, including extra and intracellular pH reductions that result in a balance of activation and inhibition of ion channels present in the membrane of neurons. The ionic mechanisms by which LC neurons respond to acidification are usually attributed to an "accelerator" whereby pH decrease causes an inhibition of K+channels or activation of Na+ and Ca+2 channels to depolarize CO2-sensitive neurons. Nonetheless, it is still unknown if this "accelerator" pathway could be controlled by a brake phenomenon. This limiting pathway (braking pathway) may represent a new mechanism to control the gain of the neurons' chemosensitive response to hypercapnic acidosis, and alterations in this pathway may contribute to pathological conditions such as sleep apnea and panic disorder. Therefore, in view of the above evidence, the purpose of this study will be to investigate the participation of KCa channels in cardiorespiratory and thermal responses during development under normoxic normocapnic and hypercapnic conditions in male and female Knockout mice for that channel. Additionally, in order to expand the knowledge, electrophysiological studies will be carried out on the chemosensitivity to CO2 of neurons from the Knockout mouse LC to the aforementioned channel. (AU)