Chronic hypoxia alters norepinephrine (NE) modulation of GABAergic inputs to second‐order neurons of peripheral chemoreceptors in the NTS

Abstract

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 α2‐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% FIO2). 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 α2‐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 α2‐AR agonist/antagonist significantly altered mIPSC amplitude. These results suggest CH attenuates NE presynaptic α2‐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.