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目的:通过研究急性缺氧对电鱼(mormyrid electric fish)小脑浦肯野细胞(Purkinje cell,PC)的功能影响,阐明缺氧耐受动物神经元在缺氧条件下的电生理特征。方法:采用全细胞膜片钳记录法,观察急性缺氧对电鱼小脑主神经元PC膜电位、兴奋性和平行纤维(parallel fiber,PF)-PC突触传递的影响。结果:(1)短暂缺氧使电鱼小脑PC膜电位发生迅速而持久的超极化,可持续30 min以上,同时伴随自发放电频率的显著下降。谷氨酸AMPA受体阻断剂CNQX不影响PC缺氧性超极化的产生,但可阻断缺氧性超极化的持续存在;而GABAA受体阻断剂Bicuculline则完全阻断缺氧性超极化的产生,并使膜电位在缺氧开始后发生短暂的去极化。(2)缺氧使PC诱发动作电位的阈值增高,频率减低,幅值减小。(3)急性缺氧使刺激PF诱发的PC兴奋性突触后电流(excitatorypostsynaptic current,EPSC)呈现长时程增强(long term potentiation,LTP),同时使EPSC双脉冲增强现象(pair-pulsefacilitation,PPF)显著衰减。CNQX逆转了PF EPSC的缺氧性LTP,表现为长时程抑制(Long Term Depression,LTD);而Bicuculline则使PF EPSC的缺氧性LTP增强。结论:耐缺氧动物电鱼小脑神经元的缺氧反应特征与哺乳类动物显著不同,AMPA受体和GABAA受体均参与电鱼小脑PC的缺氧性超极化和PF LTP的产生,表明维持GABA能突触和谷氨酸能突触活动的适度平衡,可能是电鱼以及其他耐缺氧动物脑保护机制的关键。
OBJECTIVE: To elucidate the electrophysiological characteristics of hypoxic-tolerant neurons in hypoxic conditions by studying the effects of acute hypoxia on the function of Purkinje cells (PC) in the cerebellar electric fish (mormyrid electric fish). Methods: The effects of acute hypoxia on PC membrane potential, excitability and parallel fiber (PF) -PC synaptic transmission in the primary cultured cerebellar neurons were observed by whole-cell patch clamp recording. Results: (1) Short hypoxia resulted in rapid and sustained hyperpolarization of the cerebellar PC membrane potential, which could last for more than 30 min with a significant decrease of spontaneous discharge frequency. The glutamate AMPA receptor blocker CNQX did not affect the hypoxic hyperpolarization of PC, but blocked the persistence of hypoxic hyperpolarization; while the GABAA receptor blocker Bicuculline completely blocked hypoxia Generation of hyperpolarization and transient depolarization of membrane potential after hypoxia begins. (2) Hypoxia increased the threshold of PC-evoked action potentials, decreased the frequency and decreased the amplitude. (3) Acute hypoxia induced long-term potentiation (LTP) of excitatory postsynaptic currents (EPS) in PC-stimulated PF-induced PCFs, while the two-pulse EPSP ) Significantly decayed. CNQX reverses the hypoxic LTP of PF EPSCs, which manifests as Long Term Depression (LTD), while Bicuculline increases the hypoxic LTP of PF EPSCs. CONCLUSION: The hypoxia response characteristics of the neurons in the anoxia-resistant fish are significantly different from those in mammals. Both AMPA receptor and GABAA receptor are involved in hypoxic hyperpolarization and PF LTP production in the cerebellum of electrical fish Maintaining a modest balance of GABAergic synaptic and glutamatergic synaptic activity may be the key to brain protection mechanisms in electric fish and other anaerobic animals.