The Inhibition of Inwardly Rectifying K⁺Channels by Memantine in Macrophages and Microglial Cells

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 IC₅₀ 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.

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

“…Their electrodes had a resistance of 3-5 MΩ when filled with the different pipette solution described above. Ion currents were measured in whole-cell, cell-attached or inside-out configuration of the standard patch-clamp technique using an RK-400 patch amplifier (Bio-Logic, Claix, France) [14,15,27,28]. Junctional potentials between the pipette solution and extracellular medium became nulled prior to seal formation.…”

“…TRAM-34 is known to be a selective blocker of IK Ca channels [22,29,30]. The concentration required to suppress 50% of channel activity was determined by means of a Hill function [28]:…”

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

“…Zhang et al with potassium channels to reduce the amplitude of inwardly rectifying K+ current in glioma cells and macrophage, 10,11 work as an xeroderma pigmentosum group B/transcription factor II H inhibitor to block transcriptional initiation, 12,13 and increase the production of reactive oxygen species (ROS). 14 It inhibits cell activation and cytokine gene expression and suppresses the expression of genes for transcription factors.…”

SPAK and OSR1 Sensitive Kir2.1 K⁺ Channels

“…Kir2.1 channels are expressed in neurons [87][88][89][90] and glial cells [91][92][93][94][95][96][97][98][99] and contribute to spatial K + buffering thus influencing neuronal excitability [87,94,100]. The ubiquitously expressed SPAK [101] and OSR1 similarly influence neuronal excitability, an effect, however, attributed to their effect on cytosolic Cl -concentration in neurons, which is critically important for the effect of Cl -channel opening on cell membrane potential and thus excitation [57][58][59].…”