Inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in rat supraoptic neurons: involvement in histamine-induced enhancement of depolarizing afterpotentials.
Inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in rat supraoptic neurons: involvement in histamine-induced enhancement of depolarizing afterpotentials.
复制标题
大鼠视上神经元中肌醇 1,4,5-三磷酸敏感的 Ca2 储存：参与组胺诱导的去极化后电位增强。
DOI：
10.1016/s0306-4522(99)00168-2
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
Hatton,GI
中科院分区：
文献类型：
--
作者：
Li,Z;Miyata,S;Hatton,GI
组胺是一种公认的神经调质和神经递质，可使视上神经元去极化，并增强去极化后电位，后者在决定视上神经元兴奋性方面起关键作用。本研究利用免疫组织化学和电生理学方法研究组胺诱导的去极化后电位增强中的细胞内信号转导。丰富的肌醇1，4，5-三磷酸受体相关的免疫染色被认为是在视上核的所有部分，主要是在胞体和近端过程的大细胞神经元，但也在腹侧胶质层的星形胶质细胞。在显示去极化后电位的视上神经元中，三个短暂的去极化诱发了一个缓慢的内向电流。在几乎所有测试的视上神经元中，浴用组胺（1 - 2.5 μ M）可逆地增强了这种缓慢的内向电流。慢内向电流的幅度和时程分别增加68.1%和22.8%。用组胺受体（亚型1）拮抗剂（pyrilamine）或磷脂酶C激活抑制剂（新霉素或U73122）预处理细胞，可防止组胺诱导的缓慢内向电流增强。当电极含有肝素，肌醇1，4，5-三磷酸受体阻断剂，用于记录，组胺对慢内向电流没有影响。肝素，但是，未能取消去甲肾上腺素诱导的增强慢内向电流。将蛋白激酶C抑制剂H7 [1-（5-isoquinolinylsulfonyl）-2-methylpiprazine]经电极注入视上神经元后，组胺引起的慢内向电流增强也被阻断。这些结果表明，肌醇1，4，5-三磷酸受体敏感的Ca 2+商店在视上神经元的存在和功能作用。组胺受体（亚型1）和磷脂酶C激活后，钙从内部存储动员参与介导组胺诱导的增强去极化后电位。
Histamine, a putative neuromodulator and neurotransmitter, can depolarize supraoptic neurons and enhance depolarizing afterpotentials that play a key role in determining the excitability of these neurons. This study investigated intracellular signal transduction involved in histamine-induced enhancement of depolarizing afterpotentials utilizing immunohistochemical and electrophysiological methods. Abundant inositol 1,4,5-trisphosphate receptor-related immunostaining was seen in all parts of the supraoptic nucleus, mainly within somata and proximal processes of the magnocellular neurons, but also in astrocytes of the ventral glial lamina. In supraoptic neurons displaying depolarizing afterpotentials, three brief depolarizations evoked a slow inward current. Bath application of histamine (1–2.5μM) reversibly enhanced this slow inward current in almost all supraoptic neurons tested. Amplitudes and durations of the slow inward current were increased by 68.1% and 22.8%, respectively. Pretreatment of cells with a histamine receptor (subtype 1) antagonist (pyrilamine) or inhibitors of phospholipase C activation (neomycin or U73122) prevented histamine-induced enhancement of the slow inward current. When electrodes containing heparin, an inositol 1,4,5-trisphosphate receptor blocker, were used for recording, histamine had no effect on the slow inward current. Heparin, however, failed to abolish norepinephrine-induced enhancement of the slow inward current. After H7[1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], an inhibitor of protein kinase C, was infused into supraoptic neurons via the electrodes, histamine-induced enhancement of the slow inward current was also blocked. These results indicate the presence of, and functional roles for, inositol 1,4,5-trisphosphate receptor-sensitive Ca2+stores in supraoptic neurons. Following activation of histamine receptors (subtype 1) and phospholipase C, Ca2+mobilization from internal stores participates in mediating histamine-induced enhancement of depolarizing afterpotentials.