The inhibition of inwardly rectifying K channels by memantine in macrophages and microglial cells

Ke Li Tsai, Hsueh Fen Chang, Sheng-Nan Wu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background/Aims: Memantine (MEM) can block N-methyl-D-aspartate receptors non-competitively and is recognized to exert anti-inflammatory action. Whether MEM and other related compounds produce any effects on K + currents in macrophages and in microglial cells is largely unknown. In this study, we investigated the effects of MEM and other related compounds on inwardly rectifying K + current (I K(IR) ) in RAW 264.7 macrophages and in BV2 microglial cells. Methods: Patch-clamp recordings under whole-cell, cell-attached or inside-out configuration were performed in standard patch-clamp technique. MEM suppressed the I K(IR) amplitude in a concentration-dependent manner with an IC 50 value of 12 μM. Results: This agent significantly slowed the inactivation time rate of I K(IR) evoked with membrane hyperpolarization. In cells dialyzed spermine (10 μM), MEM-mediated inhibition of I K(IR) no longer existed. MEM-suppressed activity is associated with a decrease in the slow component of mean open time and an increase in mean closed time, despite no detectable change in single-channel conductance of inwardly rectifying K + (Kir) channels. Under current-clamp conditions, the addition of MEM resulted in membrane depolarization of RAW 264.7 cells. Similarly, in BV2 microglial cells, addition of MEM suppressed I K(IR) as well as depolarized the membrane. However, neither C6 astrocytic cells nor Jurkat T-lymphoces were noted to display I K(IR) . Conclusion: The block by MEM of Kir2.1 channels is thus one of the important mechanisms underlying its actions on the functional activities of either macrophages or microglial cells, if similar findings occur in vivo.

Original languageEnglish
Pages (from-to)938-951
Number of pages14
JournalCellular Physiology and Biochemistry
Volume31
Issue number6
DOIs
Publication statusPublished - 2013 Jan 1

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Inwardly Rectifying Potassium Channel
Memantine
Macrophages
Patch-Clamp Techniques
Membranes
Jurkat Cells
Spermine
N-Methyl-D-Aspartate Receptors
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

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abstract = "Background/Aims: Memantine (MEM) can block N-methyl-D-aspartate receptors non-competitively and is recognized to exert anti-inflammatory action. Whether MEM and other related compounds produce any effects on K + currents in macrophages and in microglial cells is largely unknown. In this study, we investigated the effects of MEM and other related compounds on inwardly rectifying K + current (I K(IR) ) in RAW 264.7 macrophages and in BV2 microglial cells. Methods: Patch-clamp recordings under whole-cell, cell-attached or inside-out configuration were performed in standard patch-clamp technique. MEM suppressed the I K(IR) amplitude in a concentration-dependent manner with an IC 50 value of 12 μM. Results: This agent significantly slowed the inactivation time rate of I K(IR) evoked with membrane hyperpolarization. In cells dialyzed spermine (10 μM), MEM-mediated inhibition of I K(IR) no longer existed. MEM-suppressed activity is associated with a decrease in the slow component of mean open time and an increase in mean closed time, despite no detectable change in single-channel conductance of inwardly rectifying K + (Kir) channels. Under current-clamp conditions, the addition of MEM resulted in membrane depolarization of RAW 264.7 cells. Similarly, in BV2 microglial cells, addition of MEM suppressed I K(IR) as well as depolarized the membrane. However, neither C6 astrocytic cells nor Jurkat T-lymphoces were noted to display I K(IR) . Conclusion: The block by MEM of Kir2.1 channels is thus one of the important mechanisms underlying its actions on the functional activities of either macrophages or microglial cells, if similar findings occur in vivo.",
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The inhibition of inwardly rectifying K channels by memantine in macrophages and microglial cells. / Tsai, Ke Li; Chang, Hsueh Fen; Wu, Sheng-Nan.

In: Cellular Physiology and Biochemistry, Vol. 31, No. 6, 01.01.2013, p. 938-951.

Research output: Contribution to journalArticle

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