Elsevier

Brain Research

Volume 862, Issues 1–2, 17 April 2000, Pages 187-193
Brain Research

Research report
A function of delayed rectifier potassium channels in glial cells: maintenance of an auxiliary membrane potential under pathological conditions

https://doi.org/10.1016/S0006-8993(00)02144-2Get rights and content

Abstract

Müller glial cells from human and guinea-pig retinae were investigated using the whole-cell patch-clamp technique. Human Müller cells from eyes with different diseases were characterized by diminished inwardly-rectifying K+ currents. A comparable reduction of these currents was achieved in guinea pig Müller cells by treatment with iodoacetate to generate ischemia-like conditions. Consequently, the membrane potentials were reduced significantly in both diseased human and iodoacetate-treated guinea-pig Müller cells as compared to normal controls. However, the potentials were still clearly negative. Delayed rectifier currents could still be recorded under these conditions. Application of quinine blocked the delayed rectifier K+ channels, and resulted in a total breakdown of the membrane potentials. Thus, it becomes apparent that the glial delayed rectifier K+ channels are necessary to maintain an ‘auxiliary’ membrane potential under certain pathological conditions that are characterized by an almost total loss of inward rectifier conductance. Therefore, the delayed rectifier K+ channels of glial cells may become crucial for the support of basic glial functions.

Introduction

Glial cell membranes have previously been considered to be exclusively permeable for ‘passive’ K+ currents, i.e. currents with linear IV relationships [30]. More recently, the presence of voltage- and ligand-gated ion channels on glia has been demonstrated (see reviews in Refs. [1], [16]). In general, all principal types of voltage- and ligand-gated channels known from neuronal cells, are also found on glial cells, including Na+- and Ca2+-, as well as various types of K+ channels. The endowment of glial cells with channel types, once believed to be exclusively expressed in neurons, raises the question of what their function in glial cells may be.

Among the K+ channels described in glial cells, including Ca2+-dependent, inwardly rectifying, delayed rectifier and A-type K+ channels, a fairly clear functional concept exists only for the inwardly rectifying channels [31]. These are well known to maintain the glia-typical very negative membrane potential [31]. The high negativity of their membrane potential allows the glial cells to perform critical tasks, such as glutamate uptake via their powerful voltage-dependent glutamate transporters [21].

The function of the outwardly rectifying, voltage-dependent K+ channels (Kv channels), found in astrocytes [2], oligodendrocytes [32], Bergmann glial cells [19] and Müller cells [27], remains rather speculative. The channels have been suggested to be involved in K+ homeostasis [33] and cell proliferation [7], [31]. These channels possess a steady-state activation curve with a rather depolarized activation threshold. Thus, the question remains open how the channels can be activated in glial cells with their significantly more negative membrane potentials. Neurotransmitters released from neurons may be involved in this process, because they have been shown to depolarize glial cells [15]. However, until now there is no clear experimental evidence for the function of outwardly rectifying K+ channels in macroglial cells.

From the fact that the inwardly rectifying K+ channels are necessary to maintain the high glial membrane potential the question arises what happens under pathological conditions when the inwardly rectifying K+ conductance is significantly reduced, such as in Müller cells from pathologically altered retinae [12], in astrocytes from hippocampal epileptogenic foci [22] and in human astrocytic tumor cells [4]. This reduction is combined with reduced membrane potentials in these cells. Our hypothesis was that a special type of Kv channel, the delayed rectifier K+ channel, may be activated under such circumstances and may thus help to maintain an ‘auxiliary’ membrane potential in the glial cells.

Therefore, we used the whole-cell patch-clamp technique to study isolated Müller glial cells with inward-rectifier current reduction due to pathological conditions, and we also tested the effect of delayed rectifier blockade on the membrane potential of these cells.

Section snippets

Preparation of cells

For the present study both human and guinea-pig Müller glial cells were used. Human retinal tissue was obtained during vitreoretinal surgery to relieve retinal traction in proliferative vitreoretinopathy as well as from organ donors whose eyes served as a source for corneal transplantation. Use of human retinae was approved by the Ethics Committee of the School of Medicine, University of Leipzig. Adult guinea pigs (300–800 g body weight) were killed by urethane (>2 g/kg body weight, i.p.), the

Müller cells from diseased human retinae

Müller cells are characterized by a large K+ conductance in both inward and outward direction. As we demonstrated in a previous study [12], this current pattern changes dramatically in diseased human retinae of patients suffering from proliferative vitreoretinopathy. These cells displayed an high membrane resistance (Table 1) due to very small inwardly rectifying K+ currents (Fig. 1A,D). The membrane of these cells was significantly depolarized (Table 1). Müller cells of healthy eyes (organ

Discussion

Glial cells are characterized by a very high K+ conductance [17] which is countered only by weak depolarizing conductances, such as due to neurotransmitter receptors, stretch-activated cation channels during physiological cell swelling, and uptake of neurotransmitters via transporters [30]. However, neuronal activity is causing just weak and slow depolarizations of the glial cell membrane in the range of several millivolts [30]. This raises the question how depolarizations may be achieved that

Acknowledgements

This study was supported by grants to WR (Bundesministerium für Bildung und Forschung, 0316916A and 01ZZ9103/2.23) and to TP (University of Leipzig, Interdisciplinary Center for Clinical Research, 78990413-J4).

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