A new splice variant of large-conductance Ca2+-activated K+ (BK) channel pore subunit exhibits unique characters

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Suzuki Yoshiaki 名古屋市立大学, 薬学研究科(研究院), 助教 (80707555)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 薬理学 / 薬学 / 蛍光イメージング / パッチクランプ法 / 軟骨細胞 / BKチャネル / スプライスバリアント / 炎症

Outline of Final Research Achievements

Large-conductance Ca2+-activated K+ (BK) channels play essential roles in non-excitable cells such as chondrocytes. In the present study, functional roles of a new splice variant of the BK channel α subunit (Δe2) identified from a chondrocyte cell line, OUMS-27, were examined. Molecular image analyses revealed that Δe2 channels are not expressed on plasma membrane (PM), but can traffic to PM after forming hetero-tetramer with wild-type BKα (WT). Single-channel current analyses demonstrated that BKα hetero-tetramers containing one or two, but not three Δe2 subunits are functional. Site-directed mutagenesis identified helix2 and the linker to S1 as an essential segment for channel function. Δe2 knockdown in OUMS-27 chondrocytes increased BK current density and augmented the responsiveness to histamine assayed as COX2 gene expression. These findings provide significant new evidence that Δe2 can modulate cellular responses to physiological stimuli in human chondrocyte.

Free Research Field

薬理学