Contributions of hydrogen sulfide to synaptic neurotransmission in the nucleus of the solitary tract (nTS) in normoxia and following chronic intermittent hypoxia

Abstract

Hydrogen sulfide (H2S) is a noxious gas generated through the metabolism of cysteine by cystathionine‐β‐synthase (CBS). Data show that at low concentrations H2S can serve as a neuromodulator to regulate neurotransmission. We examined if changes in neuronal nTS excitability following chronic intermittent hypoxia (CIH) may be due, in part, to an alteration in CBS expression or function. Rats exposed to 10 days of CIH were compared to normoxic controls. Immunohistochemistry examined CBS location and distribution. Immunoblot analysis of nTS and nodose ganglia tissue examined CBS protein levels. Changes in excitatory postsynaptic currents (EPSC) in nTS neurons were recorded in brainstem slices. Immunohistochemistry showed fibrous and somal immunoreactivity in the nTS in normoxia, and suggested an increase following CIH. CBS protein was elevated after CIH in the nTS and nodose ganglia, as detected by immunoblot. In control cells, exogenous H2S significantly increased amplitude and frequency of spontaneous (s)EPSC while depolarizing the cells. Though the CBS inhibitor aminooxyacetic acid (AOA) showed no significant effects on EPSCs in control cells, following CIH AOA significantly reduced sEPSC amplitude and input resistance, and hyperpolarized the cells. These data suggest CBS is upregulated following CIH, and endogenous H2S may have a role in excitatory neurotransmission in the nTS. Supported by HL085108