A study of K(Ca) channels by using super-resolution fluorescence microscopy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07295
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Irie Tomohiko 国立医薬品食品衛生研究所, 薬理部, 主任研究官 (20546551)
• Co-Investigator(Kenkyū-buntansha): 伊藤 哲史 富山大学, 学術研究部医学系, 教授 (90334812)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: SK チャネル

Outline of Final Research Achievements

Small conductance Ca2+-activated K+ (SK) channels and large conductance potential/Ca2+-activated K+ (BK) channels are present in various neurons in the central nervous system and help regulate action potentials. In inhibitory neurons of the mammalian cochlear nucleus, both SK and BK channels are present and help regulate burst firing. In these cells, BK channels are activated by CICR via ryanodine receptors, but previous studies by the applicant had unexpectedly shown that CICR does not activate SK channels. Therefore, to identify the source of Ca2+ to SK channels, we adapted the in vitro patch-clamp technique to mouse brainstem slice preparations and conducted pharmacological experiments using voltage-gated Ca2+ (Cav) channel inhibitors. The results showed that activation of P/Q-type Cav channels is essential for SK channel opening, and that the distance between P/Q-type Cav and SK channels is relatively far (>100 nm), i.e., they form a Ca2+ microdomain.

Free Research Field

神経

Academic Significance and Societal Importance of the Research Achievements

SKチャネルは神経細胞の活動電位調節に重要な役割を果たしているが、その活性化に必要なCa２＋ソースには不明な点が残されていた。本研究では、ほ乳類蝸牛神経核の抑制性神経細胞において、SKチャネルは一般的に言われているCICRにより活性化されるのでは無く、P/QタイプCavの活性化が直接SKチャネルの活性化に関与している事を見いだした。また、P/QタイプCavとSKチャネルの距離は100ナノメートル以上と比較的離れている事、すなわちCa2+マイクロドメインを形成している事も発見した。この成果は細胞内Ca2+シグナリングに新たな知見を加えるものと考えられる。