An inhibitory role for @entity1026 -sensitive @entity2228 -gated @entity2865 channels (GlyRs) in mature hippocampus has been overlooked, largely due to the misconception that GlyR expression ceases early during development and to few functional studies demonstrating their presence. As a result, little is known regarding the physiological and pharmacological properties of native GlyRs expressed by hippocampal neurons. In this study, we used pharmacological tools and whole cell patch-clamp recordings of @entity1249 pyramidal cells and interneurons in acutely prepared hippocampal slices from 3- to 4-wk old @entity35 to characterize these understudied receptors. We show that @entity2228 application to recorded pyramidal cells and interneurons elicited @entity1026 -sensitive @entity2865 -mediated currents (I(gly)) that did not completely desensitize in the continued presence of agonist but reached a steady state at 45-60% of the peak amplitude. Additionally, the inhibitory @entity535 , @entity2226 , which has been shown to activate GlyRs in other systems, activated GlyRs expressed by both pyramidal cells and interneurons, although with much less potency than @entity2228 , having an EC(50) 10-fold higher. To examine the potential subunit composition of hippocampal GlyRs, we tested the effect of the GABA(A) receptor antagonist, @entity5094 , on I(gly) recorded from both cell types. At low micromolar concentrations of @entity5094 (< or =100 microM), which selectively block alpha homomeric GlyRs, I(gly) was partially attenuated in both cell types, indicating that alpha homomeric receptors are expressed by pyramidal cells and interneurons. At @entity5094 concentrations < or =1 mM, approximately 10-20% of the whole cell current remained, suggesting that alphabeta heteromeric GlyRs are also expressed because this subtype of GlyR is relatively resistant to @entity5094 antagonism. Finally, we examined whether hippocampal GlyRs are modulated by @entity219 . Consistent with previous reports in other preparations, @entity219 elicited a bidirectional modulation of GlyRs, with physiological @entity219 concentrations (1-100 microM) increasing whole cell currents and concentrations >100 microM depressing them. Furthermore, the same concentration of @entity219 that potentiates I(gly) suppressed currents mediated by the @entity1024 subtype of the @entity2227 receptor. Thus we provide a pharmacological characterization of native GlyRs expressed by both major neuron types in hippocampus and show that these receptors can be activated by @entity2226 , an @entity535 that is highly concentrated in hippocampus. Furthermore, our data suggest that at least two GlyR subtypes are present in hippocampus and that GlyR-mediated currents can be potentiated by @entity219 at concentrations that suppress @entity2227 -mediated excitability.

Pharmacological characterization of XXXX -gated @entity2865 currents recorded in @entity35 hippocampal slices.

@entity1026 :: ('MESH:D013331', 'Chemical') :: ['strychnine'] @entity2226 :: ('MESH:D013654', 'Chemical') :: ['taurine'] @entity1024 :: ('CHEBI:31882', 'Chemical') :: ['N-methyl-D-aspartate'] @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity2228 :: ('CHEBI:57305', 'Chemical') :: ['glycine'] @entity1249 :: ('310218(Tax:10116)', 'Gene') :: ['CA1'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity219 :: ('MESH:D015032', 'Chemical') :: ['zinc'] @entity5094 :: ('MESH:D010852', 'Chemical') :: ['picrotoxin'] @entity2865 :: ('CHEBI:17996', 'Chemical') :: ['chloride'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity2228 :: (CHEBI:57305,Chemical) :: ['glycine']
