The mechanism for the channel gating which depends on the electrochemical gradient for K+

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08509
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kurume University
• Principal Investigator: Ishihara Keiko (石原圭子) 久留米大学, 医学部, 准教授 (70265990)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: イオンチャネル / カリウムイオン / カリウムチャネル / パッチクランプ / ポリアミン / 内向き整流性

Outline of Final Research Achievements

The inward rectifier potassium (K+) channel is the background K+ channel that determines the resting potential and action potential waveform of the myocardium. The voltage dependence of this channel is said to occur by a block of the channel by impermeable intracellular cations such as polyamines. When extracellular K+ concentration is changed, the voltage-dependence of the block shifts along the voltage axis apparently depending on the electrochemical potential gradient of K+ which is determined by the potential difference and the K+ concentration difference across the membrane. The mechanism for this extracellular K+ concentration dependence is classically explained by a knock-off mechanism in which K+ ion coming from the outside competes with the blockages, and it has been considered that it does not depend on intracellular K+ concentration. In this study, however, we showed that intracellular K+ ions indeed control the block.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

医学的に血漿K+濃度の増減は特に不整脈のリスクの点で注意を要し、心電図所見は逆に血漿K+濃度の異常を知る手がかりとなることがよく知られている。これらは高あるいは低K+血症によって生じる内向き整流性K+電流の変化が心筋組織内の興奮伝播速度や再分極／活動電位持続時間などに変化をもたらすことによる。したがって内向き整流性K+チャネルが示す特異な細胞外K+濃度依存性の分子メカニズムは医学的にも重要であるが、まだ意外なほど分かっていない。本研究は今後のチャネルタンパクの構造解析や分子動力学シミュレーションを用いたその解明において必須の分子機能に関する情報を従来の電気生理学的手法を用いて明らかにした。