Author

Shuqi Mao

Publication Date

2018-05-14

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Neuroscience

Advisors

Adam C. Hall

Keywords

GABA, Glycine, Anesthesia, Inhibitory neurotransmission, Novel anesthetics, GABA-Receptors, Glycine-Receptors, Neurotransmitter receptors

Abstract

General anesthetics have become some of the most widely used therapeutic agents in medicine since they were first introduced into clinical practice. Ligand-gated ion channels are promising targets for general anesthetics. GABA and glycine receptors are two critical channels that interact with general anesthetics that potentiate inhibitory synaptic transmission in the brain. They have many similarities both structurally and functionally, leading to certain overlaps in the agents that modulate their activities. Anesthetics, such as propofol, are positive modulators of the GABAA and glycine receptors. 2,6-Di-sec-butylphenol (2,6 DSBP), a propofol analog, has been found to exhibit a higher therapeutic index than propofol. It has been shown to directly activate GABAA α1β2γ2s receptors. However, its actions on glycine receptors have yet to be characterized. The aim of this study is to further characterize the properties of DSBP as a potential novel anesthetic by evaluating its potentiation of GABA and glycine currents, its direct activation on GABAA α1β3γ2s receptors and glycine receptors, and to compare its actions on GABAA and glycine receptors. The oocytes of Xenopus laevis, the African clawed frog, were used in this study as they provide an expression system for measuring the chemical modulation of specific neurotransmitter receptors. Oocytes in this experiment were injected with receptor mRNA enabling them to express glycine and GABAA receptors. Oocytes expressing this receptor were voltage-clamped and exposed via superfusion to GABA and glycine with and without 2,6 DSBP. The results suggest that 2,6 DSBP, at the highest concentration used (100 𝜇M), enhanced currents elicited by an average of 631.2% and 173.5% for GABA and glycine respectively. 2,6 DSBP modulation was more potent on GABAA receptors than glycine receptors, suggesting that it may be more effective in inducing hypnosis rather than analgesia or immobility.

Rights

2018 Shuqi Mao. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use

Language

English

Comments

44 pages : illustrations (some color) Includes bibliographical references (pages 42-44)

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