Molecular pharmacological analyses of calcium-activated ion channels as novel drug targets

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293021
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Imaizumi Yuji 名古屋市立大学, 大学院薬学研究科, 教授 (60117794)
• Co-Investigator(Kenkyū-buntansha): 山村 寿男 名古屋市立大学, 大学院薬学研究科, 准教授 (80398362) ; 鈴木 良明 名古屋市立大学, 大学院薬学研究科, 助教 (80707555)
• Co-Investigator(Renkei-kenkyūsha): Higuchi Tsunehiko 名古屋市立大学, 薬学研究科, 教授 (50173159) ; Asai Kiyofumi 名古屋市立大学, 医学研究科, 教授 (70212462) ; Hirono Syuichi 北里大学, 薬学部, 教授 (30146328)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: イオンチャネル / 薬理学 / 薬学 / カルシウムシグナル / 創薬 / 蛍光イメージング / パッチクランプ / 生理学

Outline of Final Research Achievements

The present study revealed that in non-excitable cells such as chondrocytes andendothelial cells, Ca2+-activated K+ (KCa) channels and store-operated Ca2+ (SOC) channels play significant roles in the positive feedback mechanism for the regulation of intracellular Ca2+ concentration ([Ca2+]i). This [Ca2+]i elevation forms cellular responses to various types of stimulations in physiological conditions or gets involved in pathological process. In chondrocytes, it is demonstrated that ion channels, such as large-conductance Ca2+-activated K+ (BK) channels, Ca2+-release-activated Ca2+ (CRAC) channels, ClC-3 and ClC-7, are involved in progression of osteoarthritis. In brain capillary endothelial cells, hypoxic stress induces the up-regulation of Kir2.1, augment of positive-feedback mechanisms and promotion of cell proliferation. These events may play a role in disruption of blood-brain-barrier after cerebral hypoxia.

Free Research Field

薬理学