Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels
Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels
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DOI：
10.1089/ars.2007.1656
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发表时间：
2008-01-01
影响因子：
6.6
通讯作者：
Gutierrez-Merino, Carlos
中科院分区：
文献类型：
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作者：
Angel Garcia-Bereguiain, Miguel;Khalil Samhan-Arias, Alejandro;Gutierrez-Merino, Carlos
在细胞培养中，硫化氢（H2S）浓度可以通过重复的硫化氢钠脉冲维持在大鼠脑的范围内。在50 μ M和120 μ M的H2S浓度下（即在报道的大鼠脑H2S生理范围的上半段）暴露不到2小时，培养的小脑颗粒神经元（CGN）细胞内钙稳态发生了较大的变化，导致胞内钙浓度持续大幅升高。暴露于H2S浓度在100和300 μ M范围内仅1小时，细胞内钙升高至神经毒性范围，2小时后细胞死亡近50%。l型Ca2+通道拮抗剂尼莫地平和硝苯地平阻断H2S诱导的胞质钙升高和细胞死亡。n -甲基- d -天冬氨酸受体拮抗剂(+)-MK-801和dl -2-氨基-5-磷酸戊酸对h2s诱导的CGN死亡具有几乎完全的保护作用，并在很大程度上减轻了胞质钙的升高。因此，h2s诱导的胞质钙升高最终达到神经毒性胞质钙范围，导致谷氨酸诱导的兴奋毒性CGN死亡。作者得出结论，H2S是神经元钙稳态的主要调节剂，因为它通过l型Ca2+通道诱导Ca2+进入激活，从而激活神经元活性。
Hydrogen sulfide (H2S) concentration can be maintained in cell cultures within the range reported for rat brain by repetitive pulses of sodium hydrogen sulfide. Less than 2 h exposure to H2S concentrations within 50 and 120 mu M (i.e., within the upper segment of the reported physiological range of H2S in rat brain), produces a large shift of the intracellular calcium homeostasis in cerebellar granule neurons (CGN) in culture, leading to a large and sustained increase of cytosolic calcium concentration. Only 1 h exposure to H2S concentrations within 100 and 300 mu M raises intracellular calcium to the neurotoxic range, with nearly 50% cell death after 2 h. L-type Ca2+ channels antagonists nimodipine and nifedipine block both the H2S-induced rise of cytosolic calcium and cell death. The N-methyl-D-aspartate receptor antagonists (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid afforded a nearly complete protection against H2S-induced CGN death and largely attenuated the rise of cytosolic calcium. Thus, H2S-induced rise of cytosolic calcium eventually reaches the neurotoxic cytosolic calcium range, leading to glutamate-induced excitotoxic CGN death. The authors conclude that H2S is a major modulator of calcium homeostasis in neurons as it induces activation of Ca2+ entry through L-type Ca2+ channels, and thereby of neuronal activity.