Horning M S, Trombley P Q
Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-4340, USA.
J Neurophysiol. 2001 Oct;86(4):1652-60. doi: 10.1152/jn.2001.86.4.1652.
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 Ca(2+) 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.
锌和铜在包括嗅球和海马体在内的几个哺乳动物脑区中高度富集。从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。施加锌或铜均可消除GABA介导的自发性抑制性突触后电位。然而，与它们对抑制性传递影响的相似性相反，自发性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，但不阻止诱发的单动作电位的发放或显著改变其动力学。锌和铜对瞬时A型钾电流有不同的影响。铜仅抑制A型电流，而锌对A型电流的调节根据膜电位导致电流增强或抑制。锌和铜对钾通道的影响可能是它们对长时间阶跃去极化引起的重复发放产生影响的基础。铜降低重复发放，与初始膜电压无关。相比之下，虽然锌在与锌介导的A型电流增强相关的膜电位（-50 mV）下降低重复发放，但在相当一部分神经元中，锌在与锌介导的A型电流抑制相关的膜电位（-90 mV）下增加重复发放。施加锌或铜也抑制电压门控Ca(2+)通道，提示对神经递质释放的突触前调制可能起作用。尽管锌和铜对某些配体门控和电压门控离子通道的影响存在相似性，但这些数据表明它们的净效应可能导致对神经元兴奋性的差异调节。
