Suppression of outward K+ currents by activating dopamine D1 receptors in rat retinal ganglion cells through PKA and CaMKII signaling pathways
Suppression of outward K+ currents by activating dopamine D1 receptors in rat retinal ganglion cells through PKA and CaMKII signaling pathways
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通过 PKA 和 CaMKII 信号通路激活大鼠视网膜神经节细胞中的多巴胺 D1 受体抑制外向 K 电流
DOI：
10.1016/j.brainres.2016.01.039
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发表时间：
2016-03-15
期刊：
影响因子：
2.9
通讯作者：
Wang, Zhongfeng
中科院分区：
文献类型：
--
作者：
Li, Qian;Wu, Na;Wang, Zhongfeng
多巴胺通过激活特定的G蛋白偶联受体，对中枢神经系统的神经功能起着重要的调节作用。多巴胺D_1和D_2受体广泛分布于视网膜神经元。在本研究中，我们用膜片钳技术研究了D1R信号对急性分离的大鼠视网膜神经节细胞(RGC)外向钾电流的影响。细胞外应用D1R特异性激动剂SKF81297(10mU M)可显著且可逆地抑制细胞外向钾电流，而选择性D1R拮抗剂SCH23390(10mU M)可逆转该抑制作用。我们进一步发现SKF81297主要抑制对格列本脲(GB)和4-氨基吡啶(4-AP)敏感的钾电流成分，但对四乙基铵(TEA)敏感的钾电流成分没有影响。蛋白激酶A(PKA)和钙/钙调素依赖的蛋白激酶II(CaMKII)信号通路可能都参与了SKF81297对K+电流的抑制，因为cAMP/PKA信号抑制剂RP-cAMP(10mU M)或CaMKII特异性抑制剂KN-93(10mU M)可消除SKF81297的抑制作用。相反，蛋白激酶C(PKC)和丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)信号通路似乎都不参与，因为PKC抑制剂双吲哚马来酰亚胺(Bis IV)(10 MU M)和MAPK/ERK1/2抑制剂U0126(10 MU M)都不能阻断SKF81297诱导的K+电流的抑制。这些结果提示，D1R的激活通过细胞内PKA和CaMKII信号通路抑制大鼠视网膜节细胞对GB和4AP敏感的K+电流成分，从而调节视网膜节细胞的兴奋性。(C)2016爱思唯尔B.V.保留所有权利。
Dopamine plays an important role in regulating neuronal functions in the central nervous system by activating the specific G-protein coupled receptors. Both D1 and D2 dopamine receptors are extensively distributed in the retinal neurons. In the present study, we investigated the effects of D1 receptor signaling on outward K+ currents in acutely isolated rat retinal ganglion cells (RGCs) by patch-clamp techniques. Extracellular application of SKF81297 (10 mu M), a specific D1 receptor agonist, significantly and reversibly suppressed outward K+ currents of the cells, which was reversed by SCH23390 (10 mu M), a selective D1 receptor antagonist. We further showed that SKF81297 mainly suppressed the glybenclamide (Gb)- and 4-aminopyridine (4-AP)-sensitive K+ current components, but did not show effect on the tetraethylammonium (TEA)-sensitive one. Both protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways were likely involved in the SKF81297-induced suppression of the K+ currents since either Rp-cAMP (10 mu M), a cAMP/PKA signaling inhibitor, or KN-93 (10 mu M), a specific CaMKII inhibitor, eliminated the SKF81297 effect. In contrast, neither protein kinase C (PKC) nor mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway seemed likely to be involved because both the PKC inhibitor bisindolylmaleimide IV (Bis IV) (10 mu M) and the MAPK/ERK1/2 inhibitor U0126 (10 mu M) did not block the SKF81297-induced suppression of the K+ currents. These results suggest that activation of D1 receptors suppresses the Gb- and 4-AP-sensitive K+ current components in rat RGCs through the intracellular PKA and CaMKII signaling pathways, thus modulating the RGC excitability. (C) 2016 Elsevier B.V. All rights reserved.