Park Yong Soo, Sung Ki-Wug, Kim In-Beom
Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Function (Oxf). 2025 Feb 12;6(1). doi: 10.1093/function/zqae054.
During retinal visual processing, rod bipolar cells (RBC) transfer scotopic signals from rods to AII amacrine cells as second-order neurons. Elucidation of the RBC's excitation/inhibition is essential for understanding the visual signal transmission. Excitation mechanisms via mGluR6 and voltage-gated Ca2+ channels in the RBCs and GABAergic inhibitory synaptic inputs have been studied in previous studies. However, its intrinsic inhibitory mechanisms like K+ and Cl- channels remain unclear. We focused on RBC's prominent K+ current, which exhibits voltage and Ca2+ dependence. We isolated and confirmed the expression of intermediate-conductance Ca2+-activated K+ channels (IK) in RBCs using the patch-clamp method with IK inhibitors (clotrimazole and TRAM34) and immunohistochemistry. The regulation of the IK channel primarily relies on Ca2+ influx via low-threshold Ca2+ channels during RBC's excitation. Additionally, IK mediates late repolarization and suppresses excessive oscillation of the membrane potential in the RBCs, enabling fast and transient synaptic transmission to AII amacrine cells. Our findings highlight the unique role of the IK channel in RBCs, suggesting that it plays a critical role in the scotopic pathway by fine-tuning RBC activity.
在视网膜视觉处理过程中，视杆双极细胞（RBC）作为二阶神经元，将暗视觉信号从视杆细胞传递给AII无长突细胞。阐明RBC的兴奋/抑制对于理解视觉信号传递至关重要。先前的研究已经对RBC中通过代谢型谷氨酸受体6（mGluR6）和电压门控Ca2+通道的兴奋机制以及GABA能抑制性突触输入进行了研究。然而，其内在的抑制机制，如K+和Cl-通道，仍不清楚。我们聚焦于RBC中突出的K+电流，它表现出电压和Ca2+依赖性。我们使用膜片钳技术结合K+通道抑制剂（克霉唑和TRAM34）以及免疫组织化学方法，分离并证实了RBC中中等电导Ca2+激活K+通道（IK）的表达。IK通道的调节主要依赖于RBC兴奋期间通过低阈值Ca2+通道的Ca2+内流。此外，IK介导晚期复极化并抑制RBC膜电位的过度振荡，从而实现向AII无长突细胞的快速和瞬时突触传递。我们的研究结果突出了IK通道在RBC中的独特作用，表明它通过微调RBC活性在暗视觉通路中发挥关键作用。
