Modulation by hyperpolarization-activated cationic currents of voltage responses in human rods

Modulation by hyperpolarization-activated cationic currents of voltage responses in human rods
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DOI:
10.1016/s0006-8993(02)02531-3
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发表时间:
2002-07-05
期刊:
影响因子:
2.9
通讯作者:
Miyachi, E
Miyachi, E
中科院分区:
医学3区
文献类型:
--
作者:
Kawai, F;Horiguchi, M;Miyachi, E

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我们在手术切除的人视网膜上使用全细胞膜片钳记录技术来检测人视杆细胞感受器是否表达超极化激活的阳离子电流(I-h),并分析i-h对视杆细胞电压响应的影响。从-60 mV的保持电位开始,超极化电压阶跃在视网膜薄片和分离视杆中的两个视杆上都诱发出一种缓慢的内向整流电流。3 mM Cs+(I-h阻断剂)可显著降低超极化诱发的慢内向整流电流,而3 mM Ba2+(异常整流性K+电流阻断剂)和1 mM SITE(氯离子电流阻断剂)对超极化诱发的慢内向整流电流无明显影响。Cs~+阻断内向电流的浓度-反应曲线可用Hill方程拟合,其半数阻断浓度(IC50)为41微米,希尔系数为0.91。在所有记录电压下,内向电流激活的时间过程可用两个指数之和很好地描述。在电流钳制条件下,注入阶跃电流,无论是超极化还是去极化,都会引起最初的快速电压变化,然后是电压响应的逐渐衰减。用3mMCs+镀液消除了电压响应中的衰减。上述缓慢内向整流电流的电压依赖性、药理学和动力学表明,人的视杆表达i-h。我们认为,在强光照射产生的大的超极化过程中,i-h被激活,并可能改变人视杆细胞的光电压波形。(C)2002 Elsevier Science B.V.保留所有权利。
We used the whole-cell patch-clamp recording technique on surgically excised human retina to examine whether human rod photoreceptors express hyperpolarization-activated cationic currents (I-h) and to analyze the effects of I-h on rod's voltage responses. Hyperpolarizing voltage steps from a holding potential of -60 mV evoked a slow inward-rectifying current in both rods in retinal slices and isolated rods. The slow inward-rectifying currents induced by hyperpolarization were markedly reduced by 3 mM Cs+ (a blocker of I-h) in the bath, but not by 3 mM Ba2+ (an anomalous rectifier K+ current blocker) or 1 mM SITS (a Cl- current blocker). A concentration-response curve for block by Cs+ of the inward currents could be fitted by the Hill equation with a half-blocking concentration (IC50) of 41 muM and a Hill coefficient of 0.91. The time course of the inward current activation was well described at all recorded voltages by the sum of two exponentials. Under current-clamp conditions, injection of steps of current, either hyperpolarizing or depolarizing, elicited an initial rapid voltage change that was followed by a gradual decay in the voltage response. The decay in the voltage responses was eliminated by bath application of 3 mM Cs+. The voltage dependence, pharmacology, and kinetics of the slow inward-rectifying currents described above suggest that human rods express I-h. We suggest that I-h becomes activated in the course of large hyperpolarizations generated by bright-light illumination and may modify the waveform of the photovoltage in human rods. (C) 2002 Elsevier Science B.V. All rights reserved.