title: Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage-gated calcium currents in neurons of the subfornical organ.
abstract: Hydrogen sulfide (H2S) is an endogenously found gasotransmitter that has been implicated in a variety of beneficial physiological functions. This study was performed to investigate the cellular mechanisms underlying actions of H2S previously observed in subfornical organ (SFO), where H2S acts to regulate blood pressure through a depolarization of the membrane and an overall increase in the excitability of SFO neurons. We used whole cell patch-clamp electrophysiology in the voltage-clamp configuration to analyze the effect of 1 mM NaHS, an H2S donor, on voltage-gated potassium, sodium, and calcium currents. We observed no effect of NaHS on potassium currents; however, both voltage-gated sodium currents (persistent and transient) and the N-type calcium current had a depolarized activation curve and an enhanced peak-induced current in response to a series of voltage-step and ramp protocols run in the control and NaHS conditions. These effects were not responsible for the previously observed depolarization of the membrane potential, as depolarizing effects of H2S were still observed following block of these conductances with tetrodotoxin (5 μM) and ω-conotoxin-GVIA (100 nM). Our studies are the first to investigate the effect of H2S on a variety of voltage-gated conductances in a single brain area, and although they do not explain mechanisms underlying the depolarizing actions of H2S on SFO neurons, they provide evidence of potential mechanisms through which this gasotransmitter influences the excitability of neurons in this important brain area as a consequence of the modulation of multiple ion channels.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Kuksis
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada avf@queensu.ca.
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013356:Subfornical Organ / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D013440:Sulfides; D061566:Voltage-Gated Sodium Channels; D012964:Sodium; D002118:Calcium; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: calcium channel; hydrogen sulfide; sodium channel; subfornical organ; voltage clamp