Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular function as well as other autonomic and endocrine functions by targeting a wide range of ion channels. Using whole-cell electrophysiology, I have investigated the potential role of H2S in the regulation of neuronal excitability in the paraventricular nucleus of the hypothalamus (PVN), which is a central relay centre for autonomic and endocrine function.
In current-clamp recordings, sodium hydrosulfide hydrate (NaHS), when perfused onto PVN slices at various concentrations (0.1, 1, 10, and 50 mM), elicited a concentration-dependent response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects. Input resistance differences from baseline, and during the NaHS-induced depolarization, uncovered a biphasic response, implicating both a potassium (K+) and non-selective cation conductance.
In order to further investigate H2Ss effects on K+ conductances, we used both voltage- and current-clamp techniques to examine the effects of NaHS at either 1 or 10 mM on both the transient and sustained voltage-activated K+ currents in these neurons. We applied TEA+ (10 mM) to isolate the transient/rapidly inactivating current (IA) and 4-AP (5 mM) to isolate the sustained/delayed rectifier current (IK), and were able to show that both of these conductances were significantly reduced by H2S. Finally, we were able to demonstrate, using current-clamp, that when 4-AP and TEA+ were applied together with NaHS, they were able to completely eliminate the previously observed NaHS-induced depolarization, and the effects on membrane potential reversed to show a small hyperpolarization.
These data highlight the potential role of H2S as a critical modulator of the voltage-gated repolarizing conductances, IA and IK, which in turn regulate neuronal excitability within the PVN. This can have a large impact on the way neurotransmitters and hormones such as vasopressin, oxytocin, corticotrophin-releasing hormone, and thyrotrophin-releasing hormone are released from the PVN, which influence a wide range of neuroendocrine and autonomic functions such as cardiovascular function, fluid balance, and food intake. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-09-13 10:51:34.585
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/8293 |
| Date | 18 September 2013 |
| Creators | Khademullah, CHARLINE SAHARA |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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