Functional roles of TRPM1 channels in rod pathway of the mammalian retina

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Saitama Medical University
• Principal Investigator: Tamalu Fuminobu 埼玉医科大学, 医学部, 講師 (70337541)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 網膜 / TRPM1 / 杆体双極細胞 / AIIアマクリン細胞 / パッチクランプ / EPSC / 温度 / グルタミン酸放出

Outline of Final Research Achievements

Retinal rod bipolar cells (RBCs) depolarized approximately 20 mV as the temperature was raised from 22 ℃ to 34 ℃. Both the frequency and amplitude of EPSCs observed in the AII amacrine cells, that are post-synaptic to RBCs, increased at a higher temperature, and that the electric charge of EPSCs at 34 ℃ was about 4.3 times greater than that at 22 ℃. The increased frequency of EPSCs at 34 ℃ decreased by adding ruthenium red (RR), which is a TRP channel inhibitor. Similarly, the EPSC amplitude increased at a higher temperature, but was partially inhibited by RR. In TRPM1 KO mice, only the amplitude increased significantly at a higher temperature. Our findings indicate that the TRPM1 plays a role in the glutamate release frequency from RBCs at physiological temperature. It is likely that the body temperature may expand the dynamic range of glutamate release from RBCs by increasing the open probability of TRPM1 channel contributing to scotopic vision.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

我々の結果から、TRPM1チャネルの開口確率が体温付近で増加することで、杆体双極細胞からのグルタミン酸の放出頻度が上がり、その結果、光に対するグルタミン酸放出のダイナミックレンジが広げられていることが考えられる。杆体双極細胞は暗所視に寄与しているので、我々の研究結果は先天性の夜盲性疾患の解明などに役立つ可能性が考えられる。ただ、TRPM1チャネル単体には温度感受性がないため、細胞内リガンドやその他の細胞内因子が関連していると考えており、この点について今後明らかにしていきたい。