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GABA-Receptors, Anesthetics, Ion channels, Patch-clamp techniques (Electrophysiology), GABA, Patch-clamp
GABAA receptors are the most common inhibitory neurotransmitter receptors in the mammalian CNS and are the primary targets of the intravenous anesthetic propofol. In the presence of GABA neurotransmitter, upon binding propofol positively modulates GABAA receptor currents. This action is responsible for a temporary state of sedation and unconsciousness that is widely employed during surgery. Propofol antagonists are compounds that antagonize propofol’s potentiation of GABAergic activity. In previous work, our lab has characterized two novel anesthetic compounds, cis, trans 2,6 dimethylcyclohexanol and 2,6 diisopropylcyclohexanol, which act as weak positive modulators of GABAA receptor currents and may share a binding site with propofol on the GABAA receptor. In the current study, we use whole cell patch-clamp electrophysiology techniques to study the interactions between propofol and these novel anesthetics as they modulate GABAA receptor currents in WSS-1 cells stably expressing α1β3γ2s GABAA receptors. Although our results did not show a competitive interaction at lower doses, we did demonstrate that high concentrations of 2,6 diisopropylcyclohexanol antagonize supraclinical concentrations of propofol from directly activating GABAA receptors. These data further suggest that propofol and 2,6 diisopropylcyclohexanol may share a low affinity binding site on the GABAA receptor and compete for binding in a manner that may bring about propofol antagonism at a site responsible for propofol’s direct agonist action.
Walch, Erin M., "Characterization of cyclohexanol modulation of GABA[subscript A]" (2016). Honors Project, Smith College, Northampton, MA.
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57 pages : illustrations (some color). Honors project, Smith College, 2016. Includes bibliographical references (pages 53-55)