Depolarizing actions of hydrogen sulfide on hypothalamic paraventricular nucleus neurons.

Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of the hypothalamus (PVN) is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS) was bath applied at various concentrations (0.1, 1, 10, and 50 mM). NaHS (1, 10, and 50 mM) elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function

Hydrogen sulfide has reproducible responses and effects the various cell types in a similar manner.

<p>a) Current clamp recording trace illustrating a PVN neuron's rapid and repeatable response and recovery to 1 mM NaHS. Trace b) shows various concentrations (10 mM, 1 mM, and 0.1 mM) applied in the same neuron.</p

Hydrogen sulfide has a concentration dependent relationship.

<p>Traces illustrate the magnitude of the depolarizations in response to the various NaHS concentrations (0.1, 1, 10, and 50 mM). As the concentrations increase so does the response. a) Current clamp recording trace illustrating no response to 0.1 mM NaHS. b) Current clamp recording trace illustrating a depolarizing response to 1 mM NaHS. c) Current clamp recording trace illustrating a depolarizing response to 10 mM NaHS. d) Current clamp recording trace illustrating a depolarizing response to 50 mM NaHS, with an increase in firing frequency during the initial phase of the depolarization. e) Scatter plot showing the response of all recorded neurons to the various NaHS concentrations (0.1, 1, 10, and 50 mM) with the mean response and standard deviations indicated by the black square and bars.</p

Hydrogen sulfide-induced depolarization is biphasic.

<p>a) Current clamp recording trace illustrating the change in input resistance over the duration of the hydrogen sulfide-induced depolarization (50 mM). b) V/I plot showing the change in input resistance (point of intercept, 114 mV), during the initial phase of the depolarization. c) V/I plot showing the change in input resistance (point of intercept, 62 mV), during the recovery phase of the depolarization. Input resistance calculated from the slope of the line.</p

Hydrogen sulfide depolarizes PVN neurons.

<p>Traces illustrate the depolarizing effects of NaHS application on PVN neurons. a) Current clamp recording trace illustrating a depolarizing response to 1 mM NaHS. Trace b) shows a current clamp recording illustrating a depolarizing response to 10 mM NaHS. Bar graph c) illustrates the various responses to NaHS (0.1–50 mM) of PVN neurons (80%, n = 52/65 depolarized, 20%, n = 13/65 showed no response, and 3%, n = 2/65 hyperpolarized). Bar graph d) shows the percentage of PA (73%, n = 24/33), MNC (80%, n = 12/15), and NE (79%, n = 11/14) neurons that depolarized.</p