[Abstract Title]. - Society for Neuroscience

234. A-Type Potassium Channels
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 234.15/C39
Topic: B.04.c. Potassium channels: Physiology
Support: Thomas and Kate Jeffress Memorial Trust
HHMI Grant to the University of Richmond
Title: Determining the structural basis for fatty acid sensitivity of Kv4 potassium channels
Authors: *L. M. BOLAND, G. TIMONEY, M. DRZEWIECKI, L. M. SPICER;
Dept Biol., Univ. Richmond, Richmond, VA
Abstract: Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA; C20:4) and
docosahexaenoic acid (DHA; C22:6) modulate fast-inactivating Kv4 potassium channels which
are localized to post-synaptic dendritic regions of CNS neurons. This modulation regulates
neuronal firing frequency and the induction of hippocampal long-term potentiation. The goal of
this project is to identify structural regions of Kv4 or the Kv4/KChIP channel complex which
confer sensitivity to modulation by AA and DHA. Using a site-directed mutagenesis approach
which is guided by homology modeling, we are probing functional regions of the channel which
are involved in ionic conduction and inactivation gating. K + currents are recorded by twoelectrode
voltage clamp of Xenopus oocytes injected with subunit-specific mRNAs. A conserved
residue in the pore region of Kv4.2 was studied by mutagenesis and found to confer sensitivity to
inhibition of the peak Kv4.2/KChIP1b potassium current in voltage clamp recordings. Kinetic
modulation of gating was also reduced but not completely prevented by the pore mutation. Our
results suggest that the PUFAs may require certain amino acids in the pore region in order to
confer channel block whereas modulation of inactivation gating may be regulated by different
regions of the channel. We are currently testing other regions of interest including regions that
regulate gating in order to better understand the mechanisms of PUFA modulation of Kv4
channel function and contribute to our understanding of the impact of fatty acids as signaling
molecules. This research was supported by undergraduate fellowships from an HHMI grant to
the University of Richmond (MD & GT) and a grant from the Thomas and Kate Jeffress
Memorial Trust (LMB).
Disclosures: L.M. Boland , None; G. Timoney, None; M. Drzewiecki, None; L.M. Spicer,
None.
Poster