The Tony Kriss Visual Electrophysiology Unit, Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital/University College London, London WC1 N3JH, UK.
J Physiol. 2011 Apr 1;589(Pt 7):1681-9. doi: 10.1113/jphysiol.2010.198531. Epub 2011 Feb 7.
The K+ channel expressed by the KCNJ10 gene (Kir4.1) has previously demonstrated importance in retinal function in animal experiments. Recently, mutations in KCNJ10 were recognised as pathogenic in man, causing a constellation of symptoms, including epilepsy, ataxia, sensorineural deafness and a renal tubulopathy designated as EAST syndrome. We have studied the impact of KCNJ10 mutations on the human electroretinogram (ERG) in four unrelated patients with EAST syndrome. Corneal ganzfeld ERGs were elicited in response to flash stimuli of strengths of 0.001–10 phot cd s/m2 presented scotopically, and 0.3–10 phot cd s/m2 presented photopically. ERG waveforms from light-adapted retinae of all patients showed reduced amplitudes of the photopic negative response (PhNR) (P < 0.001). The photopic ERGs showed a delay in b-wave time to peak, but the photopic hill, i.e. the relative variation of time to peak and amplitude with luminance flash strength, was preserved. Scotopic ERGs to flash strengths 0.01 to 0.1 phot cd s/m2 showed a delay of up to 20 ms before the onset of the b-wave in two patients compared to controls. Stimulus–response functions were fitted by Michaelis–Menten equations and showed significantly lower retinal sensitivity in two patients than in controls (P < 0.001). Our study for the first time in the human ERG shows changes in association with KCNJ10 mutations affecting a Muller cell K+ channel. These data illustrate the role of KCNJ10 function in the physiology of proximal and possibly also the distal human retina.
先前的动物实验表明，由 KCNJ10 基因（Kir4.1）表达的 K+ 通道在视网膜功能中具有重要作用。最近，人们认识到 KCNJ10 突变在人类中是致病的，导致一系列症状，包括癫痫、共济失调、感觉神经性耳聋和一种称为 EAST 综合征的肾小管病。我们研究了 KCNJ10 突变对 4 名 EAST 综合征患者的人类视网膜电图（ERG）的影响。使用角膜全视野 ERG 记录系统，以 0.001–10 光 cd s/m2 的强度在暗适应下、以 0.3–10 光 cd s/m2 的强度在明适应下诱发闪光刺激。所有患者的明适应视网膜 ERG 记录到光负反应（PhNR）的振幅降低（P < 0.001）。明适应 ERG 显示 b 波的峰时延迟，但光适应 Hill 系数（即峰时和振幅与亮度闪光强度的相对变化）保持不变。与对照相比，两名患者在暗适应下对 0.01 至 0.1 光 cd s/m2 的闪光强度记录到 b 波起始前的延迟高达 20 毫秒。通过 Michaelis–Menten 方程拟合刺激-反应函数，两名患者的视网膜敏感性明显低于对照（P < 0.001）。本研究首次在人类 ERG 中显示出与 KCNJ10 突变相关的改变，这些改变影响 Muller 细胞 K+ 通道。这些数据表明 KCNJ10 功能在人类视网膜近端和可能在远端的生理功能中发挥作用。
