| Mutation
of a Pseudo Binding Site Residue (?2 Y62F) on the GABAA Receptor Eliminates
the Slow Component of Desensitization
Adam
Jansen
Carroll
College
Summer
Mentor: Dr. David A. Wagner
GABA
is the major inhibitory neurotransmitter in the vertebrate central nervous
system. The GABAA receptor is a hetero-pentameric integral membrane
protein which most commonly has a stoichiometry of 1 ? 2 ?, and 2 ? subunits.
GABA binds at the ? (+)/ ? (-) subunit interface, while the opposite?subunit
interface,? (-)/ ? (+), may be important for the process of receptor desensitization.
Data collected using rapid-ligand application methods show that macroscopic
desensitization of wild type GABAA receptor currents is a bi-phasic
process, which can be described by fitting with two exponential having
time constants (?) of approximately (fast component) and 200 ms (slow component).
Mutation of the tyrosine at position 62 of the ? 2 subunit (? 2 Y62), which
is at the ? (-)/ ? (+) interface, to phenylalanine eliminates the slow
component of desensitization and can be fit with a single exponential having
a time constant of 15 ms. These results confirm the role of the ? (-)/
? (+) interface in receptor desensitization and suggest that ? 2 Y62 is
a key residue in this process.
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