Journal
PLOS ONE
Volume 7, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0041108
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Funding
- American Epilepsy Foundation/Milken Family Foundation
- NIH [R21 DA026918]
- National Institute on Drug Abuse [R01-DA24040]
- NIDA K award [K-01DA017750]
- NINDS [R01 NS034700]
- Colorado Tobacco Research Program [1F-059]
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Kynurenic acid (KYNA), a classical ionotropic glutamate receptor antagonist is also purported to block the alpha 7-subtype nicotinic acetylcholine receptor (alpha 7* nAChR). Although many published studies cite this potential effect, few have studied it directly. In this study, the alpha 7*-selective agonist, choline, was pressure-applied to interneurons in hippocampal subregions, CA1 stratum radiatum and hilus of acute brain hippocampal slices from adolescent to adult mice and adolescent rats. Stable alpha 7* mediated whole-cell currents were measured using voltage-clamp at physiological temperatures. The effects of bath applied KYNA on spontaneous glutamatergic excitatory postsynaptic potentials (sEPSC) as well as choline-evoked alpha 7* currents were determined. In mouse hilar interneurons, KYNA totally blocked sEPSC whole-cell currents in a rapid and reversible manner, but had no effect on choline-evoked alpha 7* whole-cell currents. To determine if this lack of KYNA effect on alpha 7* function was due to regional and/or species differences in alpha 7* nAChRs, the effects of KYNA on choline-evoked alpha 7* whole-cell currents in mouse and rat stratum radiatum interneurons were tested. KYNA had no effect on either mouse or rat stratum radiatum interneuron choline-evoked alpha 7* whole-cell currents. Finally, to test whether the lack of effect of KYNA was due to unlikely slow kinetics of KYNA interactions with alpha 7* nAChRs, recordings of alpha 7*-mediated currents were made from slices that were prepared and stored in the presence of 1 mM KYNA (>90 minutes exposure). Under these conditions, KYNA had no measurable effect on alpha 7* nAChR function. The results show that despite KYNA-mediated blockade of glutamatergic sEPSCs, two types of hippocampal interneurons that express choline-evoked alpha 7* nAChR currents fail to show any degree of modulation by KYNA. Our results indicate that under our experimental conditions, which produced complete KYNA-mediated blockade of sEPSCs, claims of KYNA effects on choline-evoked alpha 7* nAChR function should be made with caution.
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