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AMPA receptors mediating glutamatergic synaptic activity in the preBötzinger Complex (PBC) OR inspiratory drive to phrenic and XII motoneurons (MNs) are differentially sensitive to UBP302
Author(s) -
Ireland Matthew Frank,
Lenal F,
Lorier Amanda,
Adachi Tadafumi,
Loomes Dustin,
Greer John,
Funk Greg D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a560-d
Subject(s) - ampa receptor , kainate receptor , glutamatergic , cnqx , neuroscience , glutamate receptor , brainstem , chemistry , excitatory postsynaptic potential , agonist , neurotransmission , slice preparation , nmda receptor , ionotropic effect , bursting , antagonist , receptor , biology , electrophysiology , biochemistry
Kainate (KA) receptors (Rs) are glutamate Rs assembled from GluR5‐7 and KA1‐2 subunits. They are widely expressed in the CNS, but their functional significance is largely unknown, due in part to a lack of selective antagonists. UBP302 is a GluR5 antagonist that is selective at concentrations 10 μM. To assess the role of GluR5 Rs in respiratory activity, UBP302 was bath‐applied to rhythmic brainstem‐spinal cord (BSSC) or medullary slice preparations. At 10 μM, it had no effect on frequency (f) of XII or C4 nerve burst amplitude. At 100 μM UB302, C4 and XII burst amplitudes fell to 0.7 ± 0.1 (BSSC; n=5) or 0.5 ± 0.1 of control, (slice; n=6). f was also unaffected by local injection of UBP302 (100 μM) into the PBC (n = 4). To confirm concentration dependence of UBP302 selectivity for KA vs AMPA Rs, we used whole‐cell voltage‐clamp recordings of XII MNs in (1 μM TTX) to assess the effects on membrane current of combinations of ATPA (KAR agonist), UBP302, AMPA, and SYM2206 (AMPAR antagonist). We defined a SYM2206‐insensitive, ATPA current (−23±5pA) that was maximally blocked by 10 μM UBP302. Also, AMPA currents were inhibited by UBP302, but only when UBP302 was >100 μM. These data indicate that XII MNs express GluR5‐containing KARs that do not contribute to inspiratory drive. Data also suggest differential involvement of AMPAR subtypes in inspiratory rhythm generation and transmission of the drive to MNs. Funding: AHFMR, CIHR, CFI, AHFMR