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Chronic hypoxia alters norepinephrine (NE) modulation of GABAergic inputs to second‐order neurons of peripheral chemoreceptors in the NTS
Author(s) -
Zhang Weirong,
Mifflin Steve
Publication year - 2008
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.22.1_supplement.1172.2
Subject(s) - yohimbine , chemoreceptor , gabaergic , inhibitory postsynaptic potential , agonist , antagonist , chemistry , medicine , endocrinology , biology , receptor
We have demonstrated that NE inhibits glutamatergic inputs to NTS receiving peripheral chemoreceptor inputs. The NE inhibition is mediated by presynaptic α‐adrenoreceptors (ARs), but it α 2 ‐AR that is responsible for the enhanced NE inhibition following chronic hypoxia (CH). We investigated the role of NE in the modulation of GABAergic inputs to NTS second‐order neurons of peripheral chemoreceptors following CH (7 days at 10% FIO 2 ). Whole‐cell recordings of NTS second‐order neurons identified by DiA labeling of carotid bodies were obtained in a brainstem slice. NE at 10μM reduced frequency of spontaneous release of GABA (mIPSCs) in the presence of TTX. NE inhibition effect was mediated by α‐ARs since α‐AR antagonist yohimbine abolished NE inhibition of mIPSC frequency (98±4% of control, n=5). CH significantly attenuated NE inhibition of mIPSC frequency (10μM NE, 27±4% vs 43±4% in normoxia, n=6 each, p <0.05). CH attenuated α 2 ‐AR agonist clonidine‐mediated inhibition of mIPSC frequency (3μM, 15±4% vs 26±1% in normoxia, n=4 each, p <0.05). Neither NE nor α 2 ‐AR agonist/antagonist significantly altered mIPSC amplitude. These results suggest CH attenuates NE presynaptic α 2 ‐AR‐mediated inhibition of GABAergic inputs to NTS neurons receiving peripheral chemoreceptor afferent inputs. The attenuated NE inhibition of GABAergic inputs could play a role in central adaptations to CH.