Dopamine activates ATP-sensitive K+ currents in rat retinal pericytes.
Dopamine activates ATP-sensitive K+ currents in rat retinal pericytes.
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DOI：
10.1017/s0952523801186104
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发表时间：
2001-11
影响因子：
1.9
通讯作者：
David M. Wu;H. Kawamura;Qing Li;D. Puro
中科院分区：
文献类型：
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作者：
David M. Wu;H. Kawamura;Qing Li;D. Puro
视网膜的相对稀疏的脉管系统使对入射光的阻碍最小化，但也对满足视网膜神经元的代谢需求提出了挑战。将能量供应分配到需要的区域的有效过程可能涉及神经源性血管活性信号。然而，毛细血管灌注的神经元-血管信号调节的机制的知识是有限的。从神经细胞释放的血管活性分子的潜在靶点是周细胞，周细胞位于微血管的内皮壁上，被认为在控制微循环中起作用。在这项研究中，我们评估了多巴胺对周细胞生理的影响。由于多巴胺能神经突与表达多巴胺受体的微血管密切相关，因此这种分子是一种假定的神经元-毛细血管信号，也是神经递质。我们使用的穿孔膜片配置的膜片钳技术监测位于新鲜分离的成年大鼠视网膜微血管的周细胞的全细胞电流。在43%（58/134）的采样周细胞中，我们发现多巴胺可逆地激活了超极化电流，使膜电位增加了19 +/- 1 mV。这种多巴胺诱导的电流被ATP敏感性钾（KATP）通道阻断剂格列本脲抑制。与涉及D1多巴胺受体、腺苷酸环化酶和蛋白激酶A（PKA）的信号通路一致，选择性D1拮抗剂SCH 23390抑制多巴胺的超极化效应;腺苷酸环化酶激活剂毛喉素模拟多巴胺能效应，而抑制PKA的H89显著降低多巴胺诱导的超极化。两者合计，我们的实验表明，涉及D1多巴胺受体，腺苷酸环化酶，PKA激活视网膜周细胞的KATP电流的机制。我们的观察结果支持这一假设，除了作为一种神经调质，多巴胺也作为一个信号连接神经元的活动与周细胞含有微血管的功能。
The relatively sparse vasculature of the retina minimizes obstruction to incoming light, but also poses a challenge to fulfilling the metabolic demands of retinal neurons. An efficient process for distributing energy supplies to areas of need is likely to involve neuron-derived vasoactive signals. However, knowledge of the mechanisms by which capillary perfusion is regulated by neuron-to-vascular signaling is limited. Potential targets of vasoactive molecules released from nerve cells are the pericytes, which are positioned on the endothelial walls of microvessels and are thought to play a role in controlling the microcirculation. In this study, we assessed the effect of dopamine on pericyte physiology. Because dopaminergic neurites are closely associated with microvessels that express dopamine receptors, this molecule is a putative neuron-to-capillary signal, as well as neurotransmitter. We used the perforated-patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on microvessels freshly isolated from the adult rat retina. In 43% (58/134) of the sampled pericytes, we found that dopamine reversibly activated a hyperpolarizing current, which increased the membrane potential by 19 +/- 1 mV. This dopamine-induced current was inhibited by the ATP-sensitive potassium (KATP) channel blocker, glibenclamide. Consistent with a signaling pathway involving D1 dopamine receptors, adenylate cyclase and protein kinase A (PKA), the selective D1 antagonist, SCH23390, inhibited the hyperpolarizing effect of dopamine; the activator of adenylate cyclase, forskolin, mimicked the dopaminergic effect, and H89, which inhibits PKA, significantly reduced the hyperpolarization induced by dopamine. Taken together, our experiments indicate that a mechanism involving D1 dopamine receptors, adenylate cyclase, and PKA activates KATP currents in retinal pericytes. Our observations support the hypothesis that, in addition to being a neuromodulator, dopamine also serves as a signal linking neuronal activity with the function of the pericyte-containing microvasculature.