Janet L. Fisher

Associate Professor

Postdoctoral Training: Univ Michigan & Baylor College of Medicine
Ph.D.: University of North Carolina - Chapel Hill
M.S.: North Carolina State University

Research Focus:

OMy lab studies the functional properties of GABAA receptors. GABAA receptors are ion channels, so we can study their activity by measuring electrical currents that pass through the receptors. The GABAA receptor has many allosteric regulatory sites, several of which are important drug targets. Modulators that increase the activity of GABAA receptors, including barbiturates and benzodiazepines, are commonly used as sedatives, anxiolytics and anti-epileptics. We study the structures within the channel that control receptor function with molecular biology techniques combined with electrophysiological recordings (patch clamp). A current project ongoing in my lab is to examine genetic mutations linked to epilepsy in humans. Many forms of epilepsy are inherited, but the underlying defects have yet to be described. A mutation in a GABAA receptor subunit was linked to inheritance of a juvenile form of epilepsy. To determine how this mutation affected the behavior of the receptor, and how it might cause seizure activity, we made the same mutation in a cloned subunit and expressed the receptors in a cell line. The results are shown below. The mutation decreased the sensitivity of the receptor to GABA, increased the deactivation rate, and decreased the channel open time. Understanding the mechanisms that lead to inherited forms of epilepsy will help us to develop more effective treatments for these disorders.

Recent Publications

• Drafts BC, Fisher JL (2006). Identification of structures within GABAA receptor alpha subunits that regulate the agonist action of pentobarbital. J Pharmacol Exp Ther 318: 1094-1101.
• Fisher JL (2004). The alpha 1 and alpha 6 subunit subtypes of the mammalian GABA(A) receptor confer distinct channel gating kinetics. J Physiol 561: 433-448.
• Picton AJ, Fisher JL (2007). Effect of the alpha subunit subtype on the macroscopic kinetic properties of recombinant GABA(A) receptors. Brain Res 1165: 40-49.
• Robinson RT, Drafts BC, Fisher JL (2003). Fluoxetine increases GABA(A) receptor activity through a novel modulatory site. J Pharmacol Exp Ther 304: 978-984.