Topographical heterogeneity of KIR currents in pericyte-containing microvessels of the rat retina:: effect of diabetes
Topographical heterogeneity of KIR currents in pericyte-containing microvessels of the rat retina:: effect of diabetes
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DOI：
10.1113/jphysiol.2006.107102
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发表时间：
2006-06-01
影响因子：
5.5
通讯作者：
Puro, Donald G.
中科院分区：
文献类型：
--
作者：
Matsushita, Kenji;Puro, Donald G.
虽然内向整流钾（K-IR）通道在动脉和小动脉中具有重要的功能作用，但对含周细胞的微血管中这些通道的了解有限。一个工作假设是，K-IR通道活动影响膜电位，从而影响近腔周细胞的收缩张力，其收缩和舒张可以调节毛细血管灌注。由于周细胞的功能被认为是特别重要的视网膜，我们使用的穿孔补丁技术，以监测离子电流的周细胞位于新鲜分离的大鼠视网膜微血管。此外，由于离子通道功能的变化可能有助于糖尿病视网膜微血管功能障碍，我们还记录了注射链脲佐菌素的大鼠含周细胞的微血管。用钡来识别K-IR电流，我们发现，有一个地形异质性，这些电流在周细胞含有微血管的正常视网膜。具体地，在远端位置处检测到的K-IR电流是强整流的，但是近端K-IR电流是弱整流的并且具有较小的内向电导。然而，在糖尿病发作后不久，这些差异随着近端K-IR电流的整流和内向电导的增加而减小。这些糖尿病引起的变化逆转的多胺合成的抑制剂，可以模仿精胺，其浓度升高，在糖尿病的眼睛。因此，精胺是介导糖尿病对微血管K-IR通道功能影响的候选者。此外，我们的研究结果提高了K-IR通道功能变化导致糖尿病视网膜血流失调的可能性。
Although inwardly rectifying potassium (K-IR) channels are known to have important functional roles in arteries and arterioles, knowledge of these channels in pericyte-containing microvessels is limited. A working hypothesis is that K-IR channel activity affects the membrane potential and thereby the contractile tone of abluminal pericytes whose contractions and relaxations may regulate capillary perfusion. Because pericyte function is thought to be particularly important in the retina, we used the perforated-patch technique to monitor the ionic currents of pericytes located on microvessels freshly isolated from the rat retina. In addition, because changes in ion channel function may contribute to microvascular dysfunction in the diabetic retina, we also recorded from pericyte-containing microvessels of streptozotocin-injected rats. Using barium to identify K-IR currents, we found that there is a topographical heterogeneity of these currents in the pericyte-containing microvasculature of the normal retina. Specifically, the K-IR current detected at distal locations is strongly rectifying, but the proximal K-IR current is weakly rectifying and has a smaller inward conductance. However, soon after the onset of diabetes, these differences diminish as the rectification and inward conductance of the proximal K-IR current increase. These diabetes-induced changes were reversed by an inhibitor of polyamine synthesis and could be mimicked by spermine, whose concentration is elevated in the diabetic eye. Hence, spermine is a candidate for mediating the effect of diabetes on the function of microvascular K-IR channels. In addition, our findings raise the possibility that functional changes in K-IR channels contribute to blood flow dysregulation in the diabetic retina.