Premium
Chronic hypoxia alters α‐adrenoreceptor modulation of synaptic transmission of peripheral chemoreceptor inputs in the NTS
Author(s) -
Zhang Weirong,
Mifflin Steve
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.21.6.a916-a
Subject(s) - phenylephrine , chemistry , chemoreceptor , hypoxia (environmental) , neurotransmission , stimulation , pharmacology , endocrinology , medicine , neuroscience , receptor , psychology , blood pressure , biochemistry , organic chemistry , oxygen
The NTS receives inputs from peripheral chemoreceptors and norepinephrine (NE) neural structures that are activated during hypoxia, suggesting a role for NE in peripheral chemoreflexes. We investigated the role of α‐adrenoreceptors (ARs) in the modulation of chemoreceptor afferent integration following exposure to chronic hypoxia (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 brain slice using electrical stimulation of tractus solitarius to evoke EPSCs (eEPSCs). NE dose‐dependently decreased the amplitude of eEPSCs and the α‐AR antagonist phentolamine (10μM) abolished NE (10μM) inhibition in both CH and normoxic (NO) cells. EC 50 of NE inhibition of eEPSCs was significantly lower in CH cells (3.1±1.2μM n=4) than in NO cells (7.9±1.1μM n=5, p <0.05). NE (10μM) elicited greater inhibition of eEPSCs in CH cells (63±4% n=6) than NO cells (36±5% n=10, p <0.01). Activation of α 1 ‐ARs with phenylephrine and α 2 ‐ARs with clonidine both decreased eEPSCs. CH significantly enhanced α 2 ‐AR inhibition (3μM clonidine, 23±2% n=5 vs. 44±5% n=4, p <0.05), but attenuated α 1 ‐AR inhibition (40μM phenylephrine, 36±3% n=10 vs. 20±5% n=6, p <0.01). NE, phenylephrine and clonidine significantly altered paired‐pulse ratio in all 45 neurons, but not holding currents and input resistance in 41/45 neurons, suggesting α‐AR inhibition is mediated via a pre‐synaptic mechanism. These results demonstrate that CH enhances NE‐induced inhibition of glutamate release in the NTS from peripheral chemoreceptor afferents via pre‐synaptic α 2 ‐ARs. The alteration of NE effect could play a role in central adaptations to CH.