Banca de DEFESA: AELTON SILVA ARAUJO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : AELTON SILVA ARAUJO
DATE: 15/05/2023
TIME: 09:00
LOCAL: https://meet.google.com/epn-zauf-vjm
TITLE:

Electrophysiological Effects of Sevoflurane in Layer 5 Pyramidal Neurons of the Mouse Primary Auditory Cortex

KEY WORDS:
PAGES: 51
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

General anesthetics are ubiquitous in medical practice, but the cellular mechanisms that promote amnesia, analgesia, immobility and unconsciousness by modulating voltage- and ligand-gated ion channels are still poorly understood. Recent studies are beginning to show the diversity of different anesthetics in regulating specific ion channels and that cortical pyramidal neurons are affected by lower concentrations than interneurons. This highlights that general anesthesia does not follow a "general" mechanism but depends on the choice of anesthetics with cell-type specific effects that need to be studied case by case. For example, the electrophysiological effects of volatile anesthetics such as sevoflurane are especially hard to study in in vitro preparations, yet, biophysical models predict stabilization of the open-state of low-threshold voltage-gated K+ channels (Kv1.2). Here we attempt a first step in identifying the electrophysiological profile of sevoflurane on layer 5 pyramidal neurons (L5 PNs) of the auditory cortex of adult mice. We applied sevoflurane by passing the carbogen mixture through a vaporizer for volatile anesthetic thereby both oxygenating and solubilizing sevoflurane in the artificial cerebrospinal fluid (aCSF) used for whole-cell patch-clamp recordings. The concentration of sevoflurane in the aCSF was quantified using gas chromatography-mass spectrometry. We further subdivided L5 PN into type A and B cells based on responses to small depolarizing and hyperpolarizing current steps, since type A and type B L5 PNs display subtle differences in membrane properties that might be modulated by sevoflurane. Quantification of passive and active membrane properties before and after application of low dose sevoflurane (approximately 22 µM) showed a decrease in the firing frequency for both cell types and a specific effect of depolarizing the action potential threshold of type A PNs, (APthreshold aCSF: -36.31 ± 0.94 mV; sevo: -21.75 ± 4.39 mV; p = 0.009; n = 8 cells) and increasing the action potential half-width of type B PNs (APHalf-width aCSF: 1.80 ± 0.13 ms; sevo: 2.29 ± 0.23 ms; p = 0.040; n = 10). Stable recordings after the washout of sevoflurane restored partially initial maximum firing frequency, AP threshold for type A and AP half-width for type B L5 PNs. Our preliminary results conclude that sevoflurane decreases the firing frequency of both types of L5 PNs, however, membrane properties are differentially affected depending on cell type. This work shows for the first time the direct effect of sevoflurane on L5 cortical pyramidal cells and adds to the cellular understanding of the mechanism of action of volatile anesthetics.

COMMITTEE MEMBERS:
Interno - 3086031 - DANIEL YASUMASA TAKAHASHI
Presidente - 1976236 - EMELIE KATARINA SVAHN LEAO
Externo à Instituição - RICARDO MAURÍCIO XAVIER LEÃO - USP