胰岛素诱导的视网膜毛细血管周细胞超极化。

Insulin-induced hyperpolarization in retinal capillary pericytes.

作者信息

Berweck S, Thieme H, Lepple-Wienhues A, Helbig H, Wiederholt M

机构信息

Department of Clinical Physiology, Universitatsklinikum Steglitz, Freie Universität Berlin, Germany.

出版信息

Invest Ophthalmol Vis Sci. 1993 Nov;34(12):3402-7.

PMID:8225875

Abstract

PURPOSE

This study investigated the mechanism of insulin-induced membrane voltage hyperpolarization in retinal capillary pericytes, which possess electrical membrane properties typical for smooth muscle cells and are supposed to regulate retinal microcirculation by a contractile mechanism.

METHODS

The mechanism of insulin-induced hyperpolarization was studied in cultured bovine retinal capillary pericytes using conventional microelectrodes.

RESULTS

Resting voltage averaged -28 +/- 0.9 mV (mean +/- SEM, n = 45). Insulin (10(-9) to 10(-7) mol/l) induced a slow hyperpolarization in a dose-dependent fashion. Voltage change (delta V) was -3.1 +/- 0.4 mV (n = 14, P < 0.0001, = control) with an insulin concentration of 10(-8) mol/l. Blockade of potassium channels with Ba2+ (5 mmol/l) completely abolished the hyperpolarizing effect of insulin (n = 5). Apamin (10(-9) mol/l), a blocker of low-conductance Ca(2+)-activated potassium channels, also completely inhibited the insulin-induced hyperpolarization (n = 4). Blocking ATP-sensitive potassium channels with glibenclamide (10(-7) mol/l) did not reduce the hyperpolarizing action of insulin (delta V = -2.2 +/- 0.4 mV, n = 5, P = 0.29). Equivalent hyperpolarizations were recorded when insulin was added in the presence of ouabain (10(-4) mol/l) to inhibit the electrogenic Na+/-/K+/-ATPase (delta V = -3.5 +/- 1.0 mV, n = 4, P = 0.68). When pericytes were grown for 3 days in culture medium with elevated glucose concentrations (22.5 mmol/l), the resting membrane voltage and the insulin-induced hyperpolarization were not significantly altered.

CONCLUSION

Insulin hyperpolarizes the membrane voltage of retinal pericytes probably mediated by activation of apamin-sensitive Ca(2+)-activated potassium channels. Therefore, hormonal modulation of membrane voltage by insulin might be an important factor in the regulation of pericyte contractility and retinal microcirculation under physiological conditions and in diabetes mellitus.

摘要

目的

本研究探讨胰岛素诱导视网膜毛细血管周细胞发生膜电压超极化的机制，视网膜毛细血管周细胞具有平滑肌细胞典型的电膜特性，并且推测其通过收缩机制调节视网膜微循环。

方法

使用传统微电极在培养的牛视网膜毛细血管周细胞中研究胰岛素诱导超极化的机制。

结果

静息电压平均为-28±0.9 mV（平均值±标准误，n = 45）。胰岛素（10⁻⁹至10⁻⁷mol/L）以剂量依赖方式诱导缓慢的超极化。胰岛素浓度为10⁻⁸mol/L时，电压变化（ΔV）为-3.1±0.4 mV（n = 14，P < 0.0001，相对于对照）。用Ba²⁺（5 mmol/L）阻断钾通道完全消除了胰岛素的超极化作用（n = 5）。蜂毒明肽（10⁻⁹mol/L），一种低电导Ca²⁺激活钾通道的阻滞剂，也完全抑制了胰岛素诱导的超极化（n = 4）。用格列本脲（10⁻⁷mol/L）阻断ATP敏感性钾通道并没有降低胰岛素的超极化作用（ΔV = -2.2±0.4 mV，n = 5，P = 0.29）。当在哇巴因（10⁻⁴mol/L）存在下加入胰岛素以抑制生电Na⁺/K⁺-ATP酶时，记录到等效的超极化（ΔV = -3.5±1.0 mV，n = 4，P = 0.68）。当周细胞在葡萄糖浓度升高（22.5 mmol/L）的培养基中培养3天时，静息膜电压和胰岛素诱导的超极化没有明显改变。