title: Hydrogen sulfide regulates intracellular Ca2+ concentration in endothelial cells from excised rat aorta.
abstract: Hydrogen sulphide (H2S) is a recently discovered gasotransmitter that may regulate a growing number of endothelial functions, including nitric oxide (NO) release, proliferation, adhesion and migration, which are the key steps of angiogenesis. The mechanism whereby H2S impacts on endothelial physiology is still unclear: however, the aforementioned processes are driven by an increase in intracellular Ca2+ concentration ([Ca2+]i). In the present study, we exploited the excised rat aorta to gain insights into the regulation of [Ca2+]i by H2S within in situ endothelial cells (ECs). Sodium hydrosulphide (NaHS), a H2S donor, caused an elevation in [Ca2+]i, which disappeared in absence of extracellular Ca2+. NaHSinduced Ca2+ inflow was sensitive to high doses of Gd3+, but not BTP-2. Inhibition of the reverse-mode of the Na+-Ca2+ exchanger (NCX), with KB-R7943 or upon removal of extracellular Na+, abrogated the Ca2+ response to NaHS. Moreover, NaHS-elicited Ca2+ entry was significantly reduced by TEA and glybenclamide, which hinted at the involvement of ATP-dependent K+ (KATP) channels. Conversely, NaHS-evoked Ca2+ signal was not affected by the reducing agent, dithiothreitol. Acute addition of NaHS hindered both Ca2+ release and Ca2+ entry induced by ATP, a physiological agonist of ECs. Consistently, inhibition of endogenous H2S synthesis with DL-propargylglycine impaired ATP-induced Ca2+ inflow, whereas it did not affect Ca2+ mobilization. These data provide the first evidence that H2S may stimulate Ca2+ influx into ECs by recruiting the reverse-mode of NCX and KATP channels. In addition, they show that such gasotransmitter may modulate the Ca2+ signals elicited by physiological stimuli in intact endothelium.
authors.affiliation: Department of Physiology, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy. francesco.moccia@unipv.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Moccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bertoni
authors.forename: Alessandra Florio
authors.initials: AF
authors.lastname: Pla
authors.forename: Silvia
authors.initials: S
authors.lastname: Dragoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pupo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Merlino
authors.forename: Daniele
authors.initials: D
authors.lastname: Mancardi
authors.forename: Luca
authors.initials: L
authors.lastname: Munaron
authors.forename: Franco
authors.initials: F
authors.lastname: Tanzi
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D002118:Calcium; D006862:Hydrogen Sulfide