Coordinate regulation of gonadotropin-releasing hormone neuronal firing patterns by cytosolic calcium and store depletion.
Coordinate regulation of gonadotropin-releasing hormone neuronal firing patterns by cytosolic calcium and store depletion.
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通过胞质钙和储备消耗协调促性腺激素释放激素神经元放电模式的调节。
DOI：
10.1073/pnas.96.7.4101
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发表时间：
1999
影响因子：
11.1
通讯作者：
Stojilkovic,SS
中科院分区：
文献类型：
--
作者：
VanGoor,F;Krsmanovic,LZ;Catt,KJ;Stojilkovic,SS
可兴奋细胞胞浆内游离钙浓度([Ca~(2+)]i)的升高通常是动作电位激发和相关的电压门控性钙内流的负反馈信号。[Ca~(2+)]升高刺激钙敏感钾通道(IK-Ca)，进而使细胞超极化，抑制Ca~(2+)内流。然而，在一些表达IK-Cas的细胞中，通过耗尽细胞内的钙离子储备物来促进电压门控的钙离子内流。在下丘脑GT1神经元细胞中，这种现象是由于促性腺激素释放激素(GnRH)受体的激活和thapsigargin抑制内质网(Ca~(2+))ATPase而引起的。GnRH引起细胞内[Ca~(2+)]i迅速升高，并伴随着短暂的超极化，随后出现持续的[Ca~(2+)]i平台，在此期间去极化细胞以更高的频率放电。短暂性超极化是由细胞内[Ca~(2+)]i的初始峰值引起的，并由apamin敏感的IK-Cachannels介导，后者也在随后的去极化阶段起作用。激动剂引起的去极化和放电增加不依赖于[Ca~(2+)]i，也不是通过抑制K~+电流而是通过易化电压不敏感的钙离子传导内向电流来实现的。由thapsigarin引起的存储耗尽也激活了这种向内的去极化电流，并增加了放电频率。因此，GT1神经元的放电模式受阿帕明敏感的SK电流和储存耗竭激活的钙电流的协调调节。这种对起搏器活动的双重控制促进了电压门控的钙离子内流，但也保护了细胞免受钙超载的影响。这一过程也可能为电压门控性钙离子内流整合到受体控制的钙离子动员提供了一般机制。
Elevation of cytosolic free Ca2+concentration ([Ca2+]i) in excitable cells often acts as a negative feedback signal on firing of action potentials and the associated voltage-gated Ca2+influx. Increased [Ca2+]istimulates Ca2+-sensitive K+channels (IK-Ca), and this, in turn, hyperpolarizes the cell and inhibits Ca2+influx. However, in some cells expressing IK-Cathe elevation in [Ca2+]iby depletion of intracellular stores facilitates voltage-gated Ca2+influx. This phenomenon was studied in hypothalamic GT1 neuronal cells during store depletion caused by activation of gonadotropin-releasing hormone (GnRH) receptors and inhibition of endoplasmic reticulum (Ca2+)ATPase with thapsigargin. GnRH induced a rapid spike increase in [Ca2+]iaccompanied by transient hyperpolarization, followed by a sustained [Ca2+]iplateau during which the depolarized cells fired with higher frequency. The transient hyperpolarization was caused by the initial spike in [Ca2+]iand was mediated by apamin-sensitive IK-Cachannels, which also were operative during the subsequent depolarization phase. Agonist-induced depolarization and increased firing were independent of [Ca2+]iand were not mediated by inhibition of K+current, but by facilitation of a voltage-insensitive, Ca2+-conducting inward current. Store depletion by thapsigargin also activated this inward depolarizing current and increased the firing frequency. Thus, the pattern of firing in GT1 neurons is regulated coordinately by apamin-sensitive SK current and store depletion-activated Ca2+current. This dual control of pacemaker activity facilitates voltage-gated Ca2+influx at elevated [Ca2+]ilevels, but also protects cells from Ca2+overload. This process may also provide a general mechanism for the integration of voltage-gated Ca2+influx into receptor-controlled Ca2+mobilization.