Simulation analysis on astrocytic K+ buffering

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: Murakami Shingo 大阪大学, 医学(系)研究科(研究院), 助教 (40437314)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アストロサイト / カリウム緩衝 / シミュレーション / システムバイオロジー / 内向き整流性カリウム電流

Outline of Final Research Achievements

In response to elevation of extracellular K+ concentration ([K+]out), astrocytes clear excessive extracellular K+ to maintain proper environment for neural activity. Here we conducted simulation analysis on the mechanisms of the astrocytic K+ clearance and swelling. Astrocyte models were constructed by incorporating into a compartment model various mechanisms. Simulated response of astrocyte models to high [K+]out revealed significant contributions of NKCC and Na,K-ATPase to the increases of the intracellular K+ and Cl- concentrations, and swelling. Moreover, we show that the KIR channel localized at synaptic cleft absorbs the excessive K+, while the K+ release through KIR channel localized at perivascular is enhanced. Further analysis of simulated drug effects shows that K+ uptake, K+ release and swelling can be modulated differently by blocking each of the ion channels and transporters.

Free Research Field

生理学