ATP-sensitive potassium channels in the control of neuronal excitability

• Grant number: 22/14196-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Ricardo Mauricio Xavier Leão
• Grantee: Ricardo Mauricio Xavier Leão
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Lucila Leico Kagohara Elias

Abstract

ATP-sensitive potassium channels (KATP) belong to the Kir6 channel family (Kir6.1 and Kir6.2 subunits), and traditionally link the energy state of the cell to the membrane potential. Its function is well characterized in pancreatic beta cells, participating in the secretion of insulin and in hypothalamic neurons that participate in the regulation of glycemia and energy metabolism, but they are present in several regions of the central nervous system unrelated to the control of energy metabolism. We have recently identified KATP channels in neurons from two regions of the brainstem, in the nucleus of the solitary tract (NTS) and in the dorsal cochlear nucleus (DCN), where they strongly control the membrane potential of these neurons and cell excitability even under normoglycemic conditions. In this project we intend to investigate in more detail how cellular energy state and neuronal activity modulate the activity of these channels in these neurons affecting neuronal excitability. We will use different concentrations of glucose, metabolic inhibitors and increased neuronal activity and will correlate with the opening or closing of these channels and their influence on membrane potential. In this way, we intend to better understand the functions of these channels in neurons in response to the cellular energy state, in addition to their traditional functions in the regulation of blood glucose. Our future results will illuminate new physiological functions of these channels with perspectives for their manipulation in situations of energy imbalance. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE SIQUEIRA, DANIELA VANESSA F.; BOARETTO, NATALIA; LEAO, RICARDO MAURICIO. Decreases in metabolic ATP open KATP channels and reduce firing in an auditory brainstem neuron: A dynamic mechanism of firing control during intense activity. Neuroscience, v. 564, p. 8-pg., 2025-01-09. (22/14196-3)