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钙激活氯电导在小鼠视杆细胞膜电位和光反应中的作用

The Role of the Ca-activated Cl Conductance in the Membrane Potential and Light Response of Mouse Rods.

作者信息

Frederiksen Rikard, Bonezzi Paul J, Fain Gordon L, Sampath Alapakkam P

机构信息

Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7000.

Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7000

出版信息

J Neurosci. 2025 May 28;45(22):e1920242025. doi: 10.1523/JNEUROSCI.1920-24.2025.

Abstract

To characterize the function of the Ca-activated Cl current in mammalian rod photoreceptors, we made patch-clamp recordings from retinal slices of mice () of both sexes that lack Ano2 (TMEM16B). Depolarizing voltage ramps in solutions blocking K currents elicited a large outward current inhibited by the Cl channel blocker niflumic acid; this current was absent in rods. The membrane potential of rods was 10-15 mV more depolarized in darkness than WT or rods, indicating a substantial resting Cl permeability. Rod outer-segment photocurrents were similar in waveform and amplitude in and rods, but photovoltages in rods were nearly doubled. Measurements of light-response reversal potentials in rods with and without Ano2 suggest that the outer-segment conductance is nearly linear with a reversal potential of -9 mV and that [Formula: see text] increases during the light response. Using these results, we estimated from permeabilized patch recordings of reversal potentials of rods to have a mean value of -35 mV near the rod resting potential, but other evidence suggests that may be more positive by as much as 10-15 mV. Thus activation of during the light response would be depolarizing. At dim intensities, the photocurrents of downstream rod bipolar cells were larger and about twice as sensitive in retinas with reduced nonlinearity. These experiments show that Ca-activated Cl currents in mammalian rods have more important roles in photoreceptor physiology than previously appreciated.

摘要

为了表征哺乳动物视杆光感受器中钙激活氯电流的功能,我们对缺乏Ano2(TMEM16B)的雌雄小鼠()的视网膜切片进行了膜片钳记录。在阻断钾电流的溶液中施加去极化电压斜坡,引发了一种被氯通道阻滞剂尼氟灭酸抑制的大外向电流;这种电流在视杆中不存在。视杆的膜电位在黑暗中比野生型或视杆去极化10 - 15 mV,表明存在大量的静息氯通透性。视杆外段光电流在和视杆中的波形和幅度相似,但视杆中的光电压几乎翻倍。对视杆有无Ano2时光反应反转电位的测量表明,外段电导几乎呈线性,反转电位为 - 9 mV,并且在光反应期间[公式:见正文]增加。利用这些结果,我们从视杆反转电位的通透膜片记录中估计,在视杆静息电位附近的平均值为 - 35 mV,但其他证据表明可能比这正10 - 15 mV之多。因此,在光反应期间的激活将使膜去极化。在低强度下,下游视杆双极细胞的光电流在非线性降低的视网膜中更大且敏感度约为两倍。这些实验表明,哺乳动物视杆中的钙激活氯电流在光感受器生理学中的作用比以前认识到的更为重要。

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