Banca de DEFESA: MARCIA PEREIRA DA SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARCIA PEREIRA DA SILVA
DATE: 28/02/2022
TIME: 09:30
LOCAL: Plataforma on-line
TITLE:

Memory analysis in ion channel kinetics. Theory and application.

KEY WORDS:

Long-term correlation; Detrended Fluctuation Analysis; Approximate Entropy; α-hemolysin; Planar Lipid Bilayer

PAGES: 70
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUMMARY:

Ion channels are integral proteins present in cell membranes responsible for ionic flux between intra and extracellular environment and between organelles and the cytoplasm. They are involved in many physiological processes, such as the generation of nerve impulses, hormone secretion, heartbeat, among countless other processes. The kinetics of ion channels is classically treated as a random process, known as the Markov process. More recently, however, several studies have shown that this process is not random, but deterministic, that is, it is history dependent. This property is called long memory or long-term correlation. However, there is still a lot of controversy as to how this property originates and which region of the channel is responsible for this property. In the present doctoral thesis, we carried out a review of the literature on memory in ion channel kinetics and published it in the journal Acta Biotheoretica, in the year 2021. In this review, the intrinsic and extrinsic factors related to the origin of long memory in channel kinetics are discussed. which models best reproduce the memory effect, which mathematical methods are used for its analysis, as well as the ubiquity of this property in different types of ion channels. In our experimental analyses, we applied the Approximate Entropy method to investigate the existence of randomness in the kinetic process of the α-hemolysin channels of Staphylococcus aureus, as well as the Detrended Fluctuation Analysis-DFA method to investigate the existence long memory in this process. These channels were incorporated into lipid bilayers composed of difitanoylphosphatidylcholine constructed by apposition of two lipid monolayers to an orifice of a partition that separates two aqueous compartments. All experiments were performed under the following conditions: 1M NaCl buffered solution, pH 4.5; voltage of 40 mV and temperature of 25 ± 1 ° C. Ionic currents in the single-channel were recorded in real time in the memory of a microcomputer coupled to an A/D converter and a patch-clamp amplifier. The mean value of the conductance of the α-hemolysin channels was 0.82 ± 0.0025 𝑛𝑆 (𝑛=128). Our results showed that the channel kinetics is a deterministic process, with the presence of long memory (𝐷𝐹𝐴𝛼= 0.63 ± 0.04) and that the Hurst exponent after data randomization was 0.51 (± 0.03), proving that the presence of long memory is a characteristic of the kinetic process of the channels and not an artifact of the numerical series. The results obtained through the approximate entropy method (𝐴𝑝𝐸𝑛𝐴=0.55142 (± 0,28; 𝐴𝑝𝐸𝑛𝐹 = 0.114472 ±0.082541) corroborate the results of the DFA method, they showed that the complexity of the original open state series tend to increase after randomization of the data, which shows that the behavior of the series has repetitions of patterns over time, indicating the presence of a deterministic dynamics. Our results showed that even simple ion channels, which are not formed by large protein domains and are not have gating domains, they also have a deterministic behavior, with the presence of long memory.

BANKING MEMBERS:
Externo à Instituição - THIAGO DE SALAZAR E FERNANDES - UFPE
Externa à Instituição - DIJANAH COTA MACHADO - UFPE
Externo à Instituição - LUIZ BEZERRA DE CARVALHO JÚNIOR - UFPE
Externo ao Programa - 1804994 - RAMON ENRIQUE RAMAYO GONZALEZ
Presidente - 1130289 - ROMILDO DE ALBUQUERQUE NOGUEIRA