Department of Physiology, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy.
Curr Pharm Biotechnol. 2011 Sep;12(9):1416-26. doi: 10.2174/138920111798281117.
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.
硫化氢（H2S）是一种新近发现的气体信号分子，可能调节越来越多的内皮功能，包括一氧化氮（NO）释放、增殖、黏附和迁移，这些都是血管生成的关键步骤。H2S 影响内皮生理学的机制尚不清楚：然而，上述过程是由细胞内 Ca2+浓度增加（[Ca2+]i）驱动的。在本研究中，我们利用离体大鼠主动脉探讨了 H2S 对内皮细胞（ECs）原位[Ca2+]i 的调节作用。作为 H2S 供体的硫氢化钠（NaHS）引起 [Ca2+]i 升高，而在无细胞外 Ca2+的情况下则消失。NaHS 诱导的 Ca2+内流对高剂量 Gd3+敏感，但对 BTP-2 不敏感。抑制 Na+-Ca2+交换器（NCX）的反向模式，用 KB-R7943 或去除细胞外 Na+，可阻断 NaHS 引起的 Ca2+反应。此外，TEA 和格列本脲显著减少了 NaHS 引起的 Ca2+内流，表明其涉及 ATP 依赖性 K+（KATP）通道。相反，还原剂二硫苏糖醇（dithiothreitol）对 NaHS 诱导的 Ca2+信号没有影响。NaHS 的急性添加抑制了由 ECs 的生理激动剂 ATP 诱导的 Ca2+释放和 Ca2+内流。一致地，用 DL-丙炔基甘氨酸抑制内源性 H2S 合成可损害 ATP 诱导的 Ca2+内流，但不影响 Ca2+动员。这些数据首次提供了证据表明 H2S 可能通过募集 NCX 的反向模式和 KATP 通道来刺激 EC 中的 Ca2+内流。此外，它们表明这种气体信号分子可能调节完整内皮细胞中生理刺激引起的 Ca2+信号。
