Frequency-dependent modulation of glycine receptor activation recorded from the zebrafish larvae hindbrain
Frequency-dependent modulation of glycine receptor activation recorded from the zebrafish larvae hindbrain
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DOI：
10.1016/j.neuroscience.2006.01.057
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Legendre, P.
中科院分区：
文献类型：
--
作者：
Rigo, J. -M.;Legendre, P.
在脊椎动物中，大多数甘氨酸抑制性神经元以相对较低的频率进行阶段性放电。这种从突触前末梢释放甘氨酸的模式可能会影响突触后甘氨酸受体的动力学。为了检查这种影响，我们分析了甘氨酸受体对连续外部电流不叠加的频率（0.5-4 Hz）重复刺激的响应行为。使用快速流动应用技术在斑马鱼后脑毛特纳细胞的外侧斑块上模拟神经递质的释放。对于应用频率：51 Hz，短时间（1 ms）重复应用饱和浓度（3 mM）甘氨酸引起的外部电流的幅度保持不变。当应用频率从 1 Hz 增加到 4 Hz 时，外部电流的幅度随着时间的推移而减小，直至达到稳态水平。随着应用频率的增加，电流幅度的下降幅度更大并且发生得更快。当刺激频率降低至 1 Hz 时发生恢复。恢复时间常数与应用频率无关。对于非饱和甘氨酸浓度也观察到这种频率依赖性抑制。我们的结果表明，当刺激频率增加到> 1 Hz 时，甘氨酸受体活性下调。使用描述斑马鱼甘氨酸受体动力学行为的简单马尔可夫模型进行的甘氨酸诱发电流模拟表明，甘氨酸受体功效的下调是由于受体在长期持续脱敏状态下的逐渐积累所致。我们的模拟表明，即使自发抑制电流以 > 1 Hz 的频率随机生成，这种下调也可能发生。 (c) 2006 年由 Elsevier Ltd 代表 IBRO 出版。
In vertebrates, most glycinergic inhibitory neurons discharge phasically at a relatively low frequency. Such a pattern of glycine liberation from presynaptic terminals may affect the kinetics of post-synaptic glycine receptors. To examine this influence, we have analyzed the behavior of glycine receptors in response to repetitive stimulation at frequencies at which consecutive outside-out currents did not superimpose (0.5-4 Hz). Neurotransmitter release was mimicked on outside-out patches from zebrafish hindbrain Mauthner cells using fast flow application techniques. The amplitude of outside-out currents evoked by short (1 ms) repetitive applications of a saturating concentration (3 mM) of glycine remained unchanged for application frequencies :51 Hz. When the application frequency was increased from 1 to 4 Hz, the amplitude of the outside-out currents decreased with time to reach a steady state level. This decrease in current amplitude was larger and occurred faster with increasing application frequencies. Recovery occurred when the stimulation frequency was decreased back to 1 Hz. The recovery time constant was independent on the application frequency. This frequency-dependent inhibition was also observed for non-saturating glycine concentrations. Our results indicate that glycine receptor activity is down-regulated when the stimulation frequency increases to values > 1 Hz. Glycine-evoked current simulations using a simple Markov model describing zebrafish glycine receptor kinetic behavior, indicates that this down-regulation of glycine receptor efficacy is due to a progressive accumulation of the receptors in a long lasting desensitization state. Our simulations suggest that this down-regulation can occur even when spontaneous inhibitory currents were generated randomly at a frequency > 1 Hz. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.