Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms
Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms
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DOI：
10.1152/jn.2001.86.4.1652
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发表时间：
2001-10-01
影响因子：
2.5
通讯作者：
Trombley, PQ
中科院分区：
文献类型：
--
作者：
Horning, MS;Trombley, PQ
锌和铜高度集中在哺乳动物的几个大脑区域，包括嗅球和海马体。对原代培养的大鼠嗅球神经元进行全细胞电生理记录，以比较锌和铜对突触传递和电压门控离子通道的影响。锌或铜的应用消除了 GABA 介导的自发抑制性突触后电位。然而，与它们对抑制传递的相似作用相反，自发的谷氨酸介导的兴奋性突触活动被铜完全阻断，但仅被锌抑制。在电压门控离子通道中，锌或铜抑制 TTX 敏感的钠通道和延迟整流型钾通道，但不能阻止诱发的单一动作电位的激发或显着改变其动力学。锌和铜对瞬态A型钾电流有明显的影响。铜仅抑制 A 型电流，而锌对 A 型电流的调节会导致电流增强或抑制，具体取决于膜电位。锌和铜对钾通道的影响可能是它们对响应长时间阶跃去极化的重复放电的影响的基础。铜减少了重复点火，与初始膜电压无关。相反，虽然锌减少了与锌介导的 A 型电流增强 (-50 mV) 相关的膜电位重复放电，但在很大一部分神经元中，锌增加了与锌介导的 A 型电流抑制 (-90 mV) 相关的膜电位重复放电。锌或铜的应用还可以抑制电压门控 Ca2+ 通道，表明神经递质释放的突触前调节可能发挥作用。尽管锌和铜对某些配体门控离子通道和电压门控离子通道的影响相似，但这些数据表明它们的净效应可能有助于神经元兴奋性的差异调节。
Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (-50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (-90 mV). Application of zinc or copper also inhibited voltage-gated Ca2+ channels, suggesting a possible role for presynaptic modulation, of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.