Role of ATP-Dependent Calcium Regulation in Modulation of Drosophila Synaptic Thermotolerance
Role of ATP-Dependent Calcium Regulation in Modulation of Drosophila Synaptic Thermotolerance
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DOI：
10.1152/jn.91209.2008
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发表时间：
2009-08-01
影响因子：
2.5
通讯作者：
Atwood, H. L.
中科院分区：
文献类型：
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作者：
Klose, M. K.;Boulianne, G. L.;Atwood, H. L.
Klose MK, Boulianne GL, Robertson RM, Atwood HL。atp依赖性钙调节在果蝇突触耐热性调节中的作用。中国生物医学工程学报（英文版）32(2):444 - 444。2009年5月27日首次发表；doi: 10.1152 / jn.91209.2008。突触传递的维持需要突触前神经末梢细胞内Ca2+的调节；在高温下失去这种调节可能会导致突触失效。因此，我们检查了果蝇幼虫神经肌肉连接处突触前钙调节的热敏性，测试破坏钙清除的影响。运动神经元加载比例Ca2+指示剂fura -葡聚糖，以监测钙随温度升高的调节。阻断Na+/Ca2+交换器或去除细胞外Ca2+阻止了常温诱导的静息钙的增加。相反，两种干扰Ca2+清除的处理——用thapsigargin使内质网Ca2+- atp酶失活和用高ph抑制质膜Ca2+- atp酶——显著加速了温度诱导的静息Ca2+浓度升高，降低了突触传递的耐热性。通过干扰能量产生破坏Ca2+- atp酶功能也促进了温度诱导的静息[Ca2+]升高和降低突触传递的耐热性。相反，通过额外的细胞内ATP强化能量水平，扩大了突触传递和Ca2+调节的工作温度范围。在每种情况下，神经电刺激引起的Ca2+升高（诱发Ca2+反应）在静息Ca2+保持在200 nM以下几分钟时失败。突触功能的失败与细胞内钙储存的释放有关，我们提供的证据表明，线粒体的释放破坏了引起的钙反应和突触传递。因此，突触传递的热极限可能与调节神经末梢细胞内离子浓度的atp依赖机制的稳定性直接相关。
Klose MK, Boulianne GL, Robertson RM, Atwood HL. Role of ATP-dependent calcium regulation in modulation of Drosophila synaptic thermotolerance. J Neurophysiol 102: 901-913, 2009. First published May 27, 2009; doi:10.1152/jn.91209.2008. Maintenance of synaptic transmission requires regulation of intracellular Ca2+ in presynaptic nerve terminals; loss of this regulation at elevated temperatures may cause synaptic failure. Accordingly, we examined the thermosensitivity of presynaptic calcium regulation in Drosophila larval neuromuscular junctions, testing for effects of disrupting calcium clearance. Motor neurons were loaded with the ratiometric Ca2+ indicator Fura-dextran to monitor calcium regulation as temperature increased. Block of the Na+/Ca2+ exchanger or removal of extracellular Ca2+ prevented the normal temperature-induced increase in resting calcium. Conversely, two treatments that interfered with Ca2+ clearance-inactivation of the endoplasmic reticulum Ca2+-ATPase with thapsigargin and inhibition of the plasma membrane Ca2+ ATPase with high pH-significantly accelerated the temperature-induced rise in resting Ca2+ concentration and reduced the thermotolerance of synaptic transmission. Disrupting Ca2+-ATPase function by interfering with energy production also facilitated the temperature-induced rise in resting [Ca2+] and reduced thermotolerance of synaptic transmission. Conversely, fortifying energy levels with extra intracellular ATP extended the operating temperature range of both synaptic transmission and Ca2+ regulation. In each of these cases, Ca2+ elevations evoked by an electrical stimulation of the nerve (evoked Ca2+ responses) failed when resting Ca2+ remained >e 200 nM for several minutes. Failure of synaptic function was correlated with the release of intracellular calcium stores, and we provide evidence suggesting that release from the mitochondria disrupts evoked calcium responses and synaptic transmission. Thus the thermal limit of synaptic transmission may be directly linked to the stability of ATP-dependent mechanisms that regulate intracellular ion concentrations in the nerve terminal.