K+ MODULATION OF MICROGLIAL SUPEROXIDE PRODUCTION - INVOLVEMENT OF VOLTAGE-GATED CA2+ CHANNELS
K+ MODULATION OF MICROGLIAL SUPEROXIDE PRODUCTION - INVOLVEMENT OF VOLTAGE-GATED CA2+ CHANNELS
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DOI：
10.1152/ajpcell.1994.266.6.c1650
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发表时间：
1994-06-01
影响因子：
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通讯作者：
GILBERT, DL
中科院分区：
文献类型：
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作者：
COLTON, CA;JIA, M;GILBERT, DL
已知在损伤和炎症过程中产生的各种细胞活性因子可以激活中枢神经系统(CNS)巨噬细胞，即小胶质细胞。由于已知中枢神经损伤部位的细胞外钾水平迅速升高，我们研究了细胞外钾的变化可能会介导小胶质细胞功能的变化。在培养的新生大鼠小胶质细胞中，研究了钾离子浓度升高对小胶质细胞超氧阴离子产生的影响。而不是直接诱导超氧阴离子的产生，暴露在含有25和55 mM钾的介质中增加了佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的超氧阴离子的产生。这种增强作用可被电压门控钙通道阻滞剂硝苯地平阻断。用电压门控钙通道激动剂Bay K 8644处理小胶质细胞，可产生与钾类似的超氧化物水平升高。因为这些数据表明存在电压门控钙通道，所以我们也检测了培养的小胶质细胞的全细胞电流。小胶质细胞暴露于Bay K 8644后，可见电压依赖性的小内向钙电流增加。通过这些通道的少量但有限的钙内流可能是调节细胞内小胶质细胞事件的一个重要因素，如NADPH氧化酶的激活和随后超氧阴离子的产生。
A variety of cytoactive factors produced during injury and inflammation are known to activate the central nervous system (CNS) macrophage, the microglia. Since extracellular potassium levels are known to rise rapidly at sites of injury in the CNS, we examined the possibility that changes in extracellular potassium could mediate changes in microglial function. The effect of an increase in potassium concentration on microglial superoxide anion production was studied in cultured neonatal rat microglia. Rather than directly inducing superoxide anion production, exposure to media containing 25 and 55 mM potassium enhanced the production of superoxide induced by phorbol 12-myristate 13-acetate. This potentiation was blocked by nifedipine, a voltage-gated calcium channel blocker. Treatment of the microglia with BAY K 8644, an agonist for voltage-gated calcium channels, produced an enhancement of superoxide levels similar to that of potassium. Because these data indicated the presence of a voltage-gated calcium channel, we also examined whole cell current in cultured microglia. A small, voltage-dependent inward calcium current was seen that was increased by exposure of the microglia to BAY K 8644. The presence of a small but finite calcium influx via these channels may be an important factor in the regulation of intracellular microglial events such as activation of the NADPH oxidase and the consequent production of superoxide anion.