Vale Carmen, Schoorlemmer Jon, Sanes Dan H
School of Medicine and Centro Regional de Investigaciones Biomedicas, University of Castilla-La Mancha, Albacete 02071, Spain.
J Neurosci. 2003 Aug 20;23(20):7516-24. doi: 10.1523/JNEUROSCI.23-20-07516.2003.
Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E(IPSC) of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.
感觉功能丧失会导致发育中的中枢神经系统内的萎缩或死亡，但对于剩余突触的生理学却知之甚少。双侧致聋后，在脑片制备中从沙鼠下丘神经元获得了短杆菌肽穿孔膜片钳记录。传入诱发的抑制性突触后电位（IPSPs）在致聋神经元中阻断电流诱发动作电位的能力减弱。这种变化部分可归因于钾依赖性氯转运功能的丧失，而钾氯共转运体的表达变化很小。抑制氯共转运的处理（布美他尼、铯和染料木黄酮）对致聋动物的神经元几乎没有影响。相同的处理使对照神经元的抑制性突触后电位平衡电位（E(IPSC)）去极化。半定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学染色表明致聋后氯共转运体mRNA或蛋白的表达没有变化。因此，严重听力损失会迅速导致氯稳态的破坏，这可能归因于钾依赖性氯共转运机制的功能障碍，而不是其表达的下调。这导致抑制性突触阻断兴奋性事件的能力降低。
