Abstract
NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.
Highlights
NG2 cells, known as polydendrocytes, represent a fourth major glial cell population in the mammalian CNS
Proton-activated currents are present in NG2 cells We investigated the functional expression of acid-sensing ion channels (ASICs) in NG2 cells using whole-cell (Fig. 3A, left) and nucleated patch (Fig. 3A, right) configurations
We have reported here that NG2-expressing cells exhibit the proton-activated current that resembles those mediated by recombinant ASICs expressed in heterologous systems [30,32] and native ASICs in many different types of hippocampal neurons [24]
Summary
NG2 cells, known as polydendrocytes, represent a fourth major glial cell population in the mammalian CNS. Unlike other types of glial cells, NG2 cells have several neuron-like properties They receive both glutamatergic and GABAergic synaptic inputs [2,3]. They express Ca2+-permeable a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) [4,5] and display long-term potentiation-like synaptic plasticity [5]. They express the synaptic vesicle protein synaptophysin [6]. They express voltage-dependent Na+ channels and generate graded spikes or action potentials [5,7,8]
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