Bachelor of Arts
Adam C. Hall
GABA, GABA-a receptor, Anesthetic, Whole-cell patch-clamp, Electrophysiology, GABA-Receptors, Patch-clamp techniques (Electrophysiology)
GABAA receptors are the most abundant inhibitory receptors in the mammalian CNS, and are the primary targets for anesthetics. General anesthetics, such as propofol, act to positively modulate the GABAA receptor and therefore enhance inhibitory signals. This allows for several events occur in the brain that alter cognition, sensation, motor responses, and autonomic control, thereby allowing an individual to undergo a medical procedure without sensation or recall of the event, (Garcia et al., 2010). Due to interest in less toxic anesthetics as well as a desire to better understand binding domains on the GABAA receptor, one focus of the Hall lab is to explore the relationship between the structure of potential anesthetics and their effect on GABAA receptor responses. Krasowski et al. (2001a) suggested that 2,6 di-sec-butylphenol has the potential to act as an anesthetic, whereas 2,6 di-tert-butylphenol does not act at GABAA receptors. However, modulation of GABAA receptors by these two structures has not been fully characterized. Previous work in the Hall lab has explored several 2,6 di-substituted cyclohexanols and revealed that these structures enhance and inhibit GABAA receptor responses in a dose dependent manner. In the current study, whole-cell patch-clamp electrophysiological techniques were used to characterize modulation and potential antagonist action of 2,6 di sec-butylphenol and 2,6 di-tert-butylphenol at the GABAA receptor in WSS-1 cells stably expressing α1β3γ2s GABAA receptors. Results indicate that, like the 2,6 di-substituted cyclohexanols, 2,6 di-sec-butylphenol acts as both an agonist and antagonist of GABAA receptor currents in a dose dependent manner. 2,6 di-tert-butylphenol was found to act mainly as an antagonist, but to a lesser extent than 2,6 di-sec-butylphenol.
2018 Madison Page Leet. 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
Leet, Madison Page, "Characterizing 2,6 Di-sec-Butylphenol and 2,6 Di-tert-Butylphenol modulation of GABAa receptor currents" (2018). Theses, Dissertations, and Projects. 2035.
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