Voltage‐gated currents expressed by rat microglia in culture

Abstract

Using the whole-cell patch-clamp technique, at least three types of voltage-gated currents expressed by cultured rat microglia were identified: an inward rectifier K+ current, a delayed rectifier K+ current (IK), and a Na+ current activated by depolarization. The inward rectifier conductance was activated by hyperpolarization to potentials more negative than -80 mV, depended on the external K+ concentration, and declined over time during whole cell recording, as the cell was internally dialyzed. The delayed rectifier current was activated by depolarization to potentials more positive than -40 mV and the rates of activation and deactivation showed a voltage-dependence similar to such currents seen in other preparations. An inward current possibly carried by Na+ was seen in a small percentage of cells. Recordings had been made from two morphological cell types, namely process-bearing ("ramified") and non-process-bearing ("ameboid"). Each of these currents was present in microglia of both morphological types. However, microglial morphology, which is thought to represent different states of activation, was significantly related to the types of combinations of currents expressed in a given cell.

Physiology of Microglia

“…With peak amplitude of ϳ50 pA, they were much smaller than in neurons. Voltage-gated Na ϩ currents were expressed only in 20% of cultured rat microglial cells; the cells with ramified morphology had a higher incidence of I Na detection (471). In contrast, in human microglial cells, cultured from explants obtained during surgery on patients suffering from brain tumors, the majority of cells (30 of 32 recorded) demonstrated TTX-sensitive I Na (658).…”

“…1) In the rat culture (471), only a subpopulation of microglial cells with a ramified morphology expressed I Na currents. It needs to be emphasized that the individually recorded cells in Korotzer's study were not identified by microglial markers and could potentially also be NG2 cells.…”

“…In microglial cells in situ and in the majority of studies in cultured microglia, rapid inward currents typical for voltage-gated sodium channels were not observed. Sodium currents (I Na ) were described in cultured microglial cells prepared from rat (471,812) and human (658) brains (see Table 2). Sodium currents in cultured microglial cells were similar to a typical neuronal Na ϩ channels; they were highly sensitive to TTX (complete inhibition at 2-5 M), had a very rapid kinetics, and had characteristic voltage dependence (threshold approximately Ϫ40 mV and peak ϳ0 mV).…”

Human neural stem cells: electrophysiological properties of voltage-gated ion channels

“…In particular, expression of K þ channels in neural membranes has been related to maintenance of a variety of cellular activities, including setting the resting membrane potentials, repolarizing/hyperpolarizing cells, and buffering extracellular K þ [4,5]. As such, expression of a certain ion channel would provide a functional marker for the neural precursor cells.…”

A Kv1.5 to Kv1.3 Switch in Endogenous Hippocampal Microglia and a Role in Proliferation

“…Most studies of microglia have used dissociated cultures, and Kv current expression has been highly variable (Eder, 1998): from no detectable current (Kettenmann et al, 1990Brockhaus et al, 1993) to substantial current (Korotzer and Cotman, 1992;Norenberg et al, 1994;Schlichter et al, 1996). The hypothesis that Kv current is absent from resting cells (Kettenmann et al, 1990;Brockhaus et al, 1993) and upregulated by microglial activation (Norenberg et al, 1994;Fischer et al, 1995;Visentin et al, 1995;Gebicke-Haerter et al, 1996) has been challenged because ramified microglia, widely believed to represent resting cells, express a prominent Kv current when exposed to astrocytes or astrocyte-conditioned medium (Schmidtmayer et al, 1994;Eder et al, 1997).…”