The Effects of Hydrogen Sulfide on Neurons in the Nucleus of the Solitary Tract

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter that has recently been described to affect the membrane potential of neurons in a number of brain areas. Using whole cell patch-clamp electrophysiological techniques, I investigated whether the H2S donor, sodium hydrosulfide (NaHS) affects the membrane potential of neurons in the nucleus of the solitary tract, an autonomic nucleus where NaHS has previously shown to effect blood pressure and heart rate. Bath application of NaHS (1 mM, 5 mM and 10 mM) to 300 µm coronal NTS brain slices led to a clear reversible depolarization in 95% of neurons tested (72/76), and in 64% (46/72) of these responding neurons was followed by a longer lasting hyperpolarization. These effects on membrane potential were found to be concentration-dependent. Furthermore, in the presence of the voltage-gated sodium channel antagonist tetrodotoxin (TTX) and the glutamate receptor antagonist kynurenic acid (KA), the depolarizing effects of 5 mM NaHS (5.0 ± 2.2 mV (n=7)) were still observed, although they were significantly reduced compared to regular aCSF (7.7 ± 2.0 mV (n=7), p *< 0.05, paired t-test). These observations support the conclusion that NaHS has both pre and post-synaptic effects which contribute to controlling the excitability of NTS neurons. I also tested the hypothesis that hyperpolarizations in response to 5 mM NaHS resulted from modulation of the KATP channel by comparing effects observed following the KATP channel blocker glibenclamide (-1.9 ± 0.9 mV (n=8)) with those recorded in control conditions (-7.9 ± 1.2 mV n=8, p* < 0.05, paired t-test). This nearly complete loss of hyperpolarizing effects in the presence of glibenclamide identifies a primary role for the KATP channel in the NaHS induced hyperpolarization of NTS neurons. Thus, the H2S donor, NaHS causes two responses in NTS neurons. These effects were found to be in part post-synaptic and the KATP channel was found to play a role in the NaHS induced hyperpolarization. This study has for the first time described post-synaptic effects of this gasotransmitter on the membrane potential of NTS neurons and thus implicates this transmitter in regulating the diverse autonomic systems controlled by these NTS neurons.