1 Departments of Pharmacology II and 2 Otolaryngology and Sensory Organ Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871; and 3 Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Glial cells express inwardly rectifying K+ (Kir) channels, which play a critical role in the buffering of extracellular K+. Kir4.1 is the only Kir channel so far shown to be expressed in brain glial cells. We examined the distribution of Kir4.1 in rat brain with a specific antibody. The Kir4.1 immunostaining distributed broadly but not diffusely in the brain. It was strong in some regions such as the glomerular layer of the olfactory bulb, the Bergmann glia in the cerebellum, the ependyma, and pia mater, while little activity was detected in white matter of the corpus callosum or cerebellar peduncle. In the olfactory bulb, Kir4.1 immunoreactivity was detected in a scattered manner in about one-half of the glial fibrillary acidic protein-positive astrocytes. Immunoelectron microscopic examination revealed that Kir4.1 channels were enriched on the processes of astrocytes wrapping synapses and blood vessels. These data suggest that Kir4.1 is expressed in a limited population of brain astrocytes and may play a specific role in the glial K+-buffering action.
glia; potassium-buffering action; immunohistochemistry; electron microscopy
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
NEURAL TISSUES consist of two major classes of cells, neurons and glial cells (4). Glial cells surround the cell bodies, dendrites, and axons of neurons and fill up the interneuronal spaces. Neuronal excitation causes an accumulation of extracellular K+ especially at synaptic sites in the central nervous system, which if uncorrected would result in cessation of synaptic transmission by depolarizing the membrane. Astrocytes are thought to transport K+ from regions of high K+ to those of low K+. This regulatory function was first proposed as a spatial buffering mechanism of astrocytes in the optic nerves (29). It was also termed the potassium siphoning in Müller cells of the retina (27).
One of the characteristic features of glial cells is their high K+ conductance (19). The high K+ conductance is thought to be critical for glial K+-buffering action. Several types of inwardly rectifying K+ (Kir) channels have been electrophysiologically identified in retinal Müller cells (6, 15, 21, 28), oligodendrocytes (24), and glioma cells (7). Previously, we showed that the mRNA of an inwardly rectifying K+ channel, Kir4.1 (5), was expressed predominantly in glial cells in rat brain (36) and that the channel protein was actually expressed in retinal Müller cells and enriched in the membrane domains that abut the vitreous body and blood vessels (15, 26). It was recently shown immunohistochemically that Kir4.1 is actually expressed in brain glial cells (31), although no information is available concerning the subcellular localization of Kir4.1 channels in brain glial cells.
In this study, immunohistochemical techniques showed that Kir4.1 was expressed in astrocytes in certain areas of rat brain. The immunoelectron microscopic study of the olfactory bulb clearly showed that Kir4.1 was mainly localized in the membrane of astrocyte processes surrounding the reciprocal synapses and blood vessels, while labeling on astrocyte processes at the excitatory synapses was rarely detected. These data indicate that Kir4.1 is mainly used for K+ buffering at a specific population of synapses.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Animals. All experiments were carried out in accordance with the Guidelines for the Use of Laboratory Animals of Osaka University Medical School. Male Wistar rats weighing between 200 and 250 g (Kiwa-jikken-dobutsu, Wakayama, Japan) were used in this study. The animals were fed and allowed access to water freely.
Antibodies. The affinity-purified anti-Kir4.1 antibody (anti-KAB-2C2) has been extensively characterized in previous studies from this laboratory (11, 12, 15, 16, 20). Rabbit polyclonal anti-glial fibrillary acidic protein (GFAP) antibody was purchased from DAKO (Carpinteria, CA).
Immunohistochemistry of rat brain. The rats were deeply anesthetized with pentobarbital sodium (50 mg/kg ip) and perfused transcardially with 4% (wt/vol) paraformaldehyde in 0.1 M sodium phosphate buffer (PB), pH 7.4 (fixative A). The brains were dissected, postfixed in the same solution at 4°C for over 48 h, and stored in 30% (wt/vol) sucrose in phosphate-buffered saline (PBS) at 4°C overnight and frozen in optimum cutting temperature (OCT) compound (Sakura, Tokyo, Japan). Sagittal and coronal sections (30 and 14 µm, respectively) were cut on a cryostat and thaw-mounted on silane-coated slides. Samples were washed five times with 0.1% (wt/vol) Triton X-100 in PBS (PBST) for 30 min each and pretreated with PBS containing 5% (wt/vol) bovine serum albumin (BSA) and 5% (vol/vol) normal goat serum (NGS) and 0.05% (wt/vol) sodium azide (solution A) at 4°C overnight to reduce nonspecific immunostaining. The sections were incubated with anti-KAB-2C2 antibody (0.19 µg/ml) in solution A at 4°C overnight. The sections were washed five times with PBST at room temperature for 30 min each and incubated with secondary antibody, and color development was carried out using the Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA). The localization of Kir4.1 immunoreactivity was visualized with 3,3'-diaminobenzidine (DAB) and nickel ammonium-H2O2 solution. The brain sections were double stained with anti-GFAP and anti-KAB-2C2 antibodies. Briefly, pretreatment and incubation with rabbit polyclonal anti-GFAP antibody was processed as described above. The sections were washed five times with PBST at room temperature for 30 min each and visualized with Texas red-labeled anti-rabbit IgG (Protos Immunoresearch, San Francisco, CA) in solution A. After incubation with Texas red-labeled antibody and washing with PBST, the sections were incubated with fluorescein isothiocyanate (FITC) (EY Laboratories, San Mateo, CA)-labeled anti-rabbit IgG-tagged anti-KAB-2C2 antibody and examined with a confocal microscope (MRC-1024, Bio-Rad, Hertfordshire, UK).
Electron microscopic analysis of rat brain. After fixation with fixative A containing 0.1% (vol/vol) glutaraldehyde, the brains were postfixed in the same solution at 4°C overnight and were cut into 50-µm slices with a vibratome. The vibratome sections were pretreated with PBST containing 3% BSA and 3% NGS and 0.05% sodium azide (solution B) and incubated with anti-KAB-2C2 antibody (3.75 µg/ml) diluted in solution B at 4°C for 48 h. Sections were then washed with PBS five times for 30 min each and were placed in biotinylated goat anti-rabbit IgG for 24 h at 4°C. The immunoreactivity was visualized by a reaction with DAB and platinous potassium chloride. Sections were washed with PBS at 4°C overnight and postfixed in reduced osmium for 1 h at 4°C. After dehydration in ethanol and infiltration of epoxy resin, sections were flat-embedded on the siliconized slide glasses. Small blocks, selected by light microscopical inspection, were cut out, glued to blank epoxy, and sectioned with an ultramicrotome. The ribbons of thin sections (thickness 70 nm) were collected on grids and counterstained with uranyl acetate and Reynold's lead citrate. These were examined with a transmission electron microscope (H7100TE, Hitachi, Tokyo, Japan).
Quantitative analysis.
The proportion of synapses, which were surrounded by immunopositive
cell membranes for Kir4.1, was assessed directly in the electron
microscope by analyzing randomly selected grid squares. We took
photographs and classified synapses morphologically into excitatory or
reciprocal based on established criteria (13, 25, 38, 39).
The distribution of Kir4.1-positive astrocytic processes surrounding
each synapse was quantified as follows: Kir4.1(++) is to indicate that
more than 60% of the synapse membrane was covered by the
Kir4.1-immunopositive cell membranes, Kir4.1(+) represents between 30 and 60%, and Kir4.1() represents <30%. [For examples of
Kir4.1(++) synapses, see Fig. 4, B, C, and E; for
an example of a Kir4.1(
) synapse, see Fig. 4D.]
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Selective expression of Kir4.1 in astrocytes and ependymal cells of
rat brain.
The specificity of the anti-Kir4.1 antibody has been extensively
characterized in our previous studies (11, 12, 15, 16,
20). Immunohistochemical studies using this antibody revealed that Kir4.1 distributed broadly but not diffusely in all brain regions
including forebrain, midbrain, and hindbrain (Fig.
1A and Table
1). The antibody that had been
preabsorbed with the immunizing peptide showed no labeling (data not
shown). The immunoreactivity was detected in the gray matter containing
neurons and astrocytes but not in the white matter mainly consisting of
myelin sheath and oligodendrocytes. In gray matter, the strongest
staining was detected in the glomerular layer of the olfactory bulb,
the molecular layer of the cerebellum, and the spinal trigeminal
nucleus, where Kir4.1 immunoreactivity was detected in the spaces
surrounding the cell bodies and dendrites of neurons. Neuronal cell
bodies were consistently unlabeled.
|
|
Studies of Kir4.1 immunoreactivity in olfactory bulb. We chose the olfactory bulb area for further detailed studies of the distribution of Kir4.1 immunoreactivity for the following reasons: 1) the olfactory bulb exhibited very strong Kir4.1 immunoreactivity (Fig. 1A), 2) it possesses a highly organized and laminated structure, and 3) the distribution of each subtype of astrocyte in this area is known (1).
Figure 2 shows immunostaining of Kir4.1 (green) and GFAP (red). GFAP is an intermediate filament specific to astrocytes (4). At lower magnification (Fig. 2A) prominent yellow signals, which suggest the localization of Kir4.1 and GFAP in close vicinity, were detected in the glomerular layer and to a lesser extent in the external plexiform layer. In the olfactory nerve layer, the signals were scarce (Fig. 2A). Because the olfactory nerve layer was prominently stained red, it would seem that GFAP-positive astrocytes in this area might not express significant amounts of Kir4.1. These immunofluorescent results were consistent with those obtained with DAB staining (Fig. 1B).
|
Subcellular localization of Kir4.1 in astrocytes.
To examine the subcellular localization of Kir4.1 in astrocytes,
immunoelectron microscopic study was performed in various regions of
the olfactory bulb (see Figs. 3 and 4). Figure
3 exhibits low-magnification images of
the olfactory nerve layer (A), the edge of the glomerular
layer (B), the inside of a glomerulus (C), and
the granule cell layer (D). Figure
4 shows higher-magnified images at the
glomerular layer (A, B, D, and E) and at the
external plexiform layer (C).
|
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The main findings in this study are as follows. 1) The inwardly rectifying K+ channel subunit Kir4.1 was expressed in about one-half of the brain astrocytes but not in neurons. 2) Kir4.1 was enriched in the membrane of astrocytic processes surrounding synapses and blood vessels. 3) At least in the olfactory bulb, the heterogeneity of Kir4.1 expression in astrocytic processes seemed to depend on the types of synapse, i.e., preferentially at reciprocal but not at excitatory synapses. 4) Kir4.1 was absent in oligodendrocytes. Therefore, Kir4.1 seems to be responsible for the K+-buffering action mediated by a specific population of astrocytes in brain.
One of the important roles of astrocytes in the brain is the spatial buffering or siphoning of K+ after neural excitation (29). This removal of K+ from the extracellular space is considered to occur mainly through Kir channels in astrocyte membranes (27), although the contributions of other K+ channels and K+ transporters are also indicated (37). Actually, Kir channels have been identified electrophysiologically in astrocytes in the central nervous system and retinal Müller glial cells (2, 28). Kir4.1 is the only Kir channel so far identified at the molecular level in brain glial cells. Our previous in situ hybridization analysis (36) indicated that Kir4.1 mRNA was expressed not only in astrocytes but also in white matter of the cerebellum, the sensory root of the trigeminal ganglion, the middle cerebellar peduncle, and the corpus callosum. In this study, significant immunoreactivity of Kir4.1 was detected only in the astrocytes in various regions of brain but not in either white matter by immunohistochemistry (Fig. 1A) or in oligodendrocytes by the electron microscopic study (Fig. 3B). Although Poopalasundaram et al. (31) showed the Kir4.1 immunoreactivity in cultured oligodendrocytes, they did not detect it in situ in the deep cerebellar nuclei of brain. We further confirmed with the immunoelectron microscopy the absence of Kir4.1 immunoreactivity in the oligodendrocytes (including the Ranvier node regions) and also in other areas of rat brain such as the cerebellar cortex, hippocampus, and cerebellum (not shown). There are a number of members of the Kir4.0 subfamily, such as mouse Kir4.2 (Ref. 10; GenBank accession no. AJ012368), salmon Kir4.3/sWIRK (Ref. 18; GenBank accession no. D83537), guinea pig Kir4.2/Kir1.3 (Ref. 9; GenBank accession no. AS049076), and human Kir4.1/Kir1.2 and Kir4.2/Kir1.3 (Ref. 34, GenBank accession no. U73191-3). There exists high homology at the nucleotide level between rat Kir4.1 and other Kir4.0 channels in the region that was used as the probe in our previous in situ hybridization analysis. The probe for our in situ hybridization exhibited 70% nucleotide identity with mouse Kir4.2, 73% with salmon Kir4.3/sWIRK, 74% with guinea pig Kir4.2/Kir1.3, 89% with human Kir4.1/Kir1.2, and 74% with human Kir4.2/Kir1.3. Therefore, in our previous in situ hybridization study we might have detected signals of not only Kir4.1 but also other members of Kir4.0.
It has been suggested from electrophysiological evidence that functional Kir channels are localized mainly in the processes of type-1 astrocytes (2) and in O-2A progenitors (3). This immunoelectron microscopic study for the first time showed morphologically that this is actually the case. We showed that the Kir4.1-enriched brain astrocyte processes surrounded synapses and blood vessels, while expression of Kir4.1 on the cell body membrane was small. This specific localization suggests that this Kir channel can carry both K+-uptake current in astrocytes at synaptic sites and K+-extrusion current to the blood vessels. Therefore, this study provides a morphological basis to support the notion that Kir4.1 is responsible for the glial K+ spatial buffering in brain. However, because not all of the astrocytes expressed Kir4.1, the Kir channel cannot entirely explain K+ spatial buffering in brain. Other mechanisms involving other K+ channels and K+ transporters may also exist in brain astrocytes.
In rat hippocampus, it was reported that astrocytes exhibit a wide range of resting membrane potentials, which is not related to developmental factors such as fetal bovine serum, length of culture, cellular morphology, and the electrophysiological techniques used (23). At least three electrophysiologically distinct types of astrocytes could be identified in the mature hippocampus (8). The expression level of Kir4.1 might be related to the divergent electrophysiological properties of astrocytes in brain. Recently, Zhou and Kimelberg (41) have reported the heterogeneous expression of Kir channels in astrocytes freshly isolated from hippocampus by electrophysiological measurements. They have classified the astrocytes into two classes, namely, variably rectifying astrocytes (VRA) and outwardly rectifying astrocytes. Only VRA showed abundant inward K+ currents (IKin) and a robust K+ uptake capability upon an increase (from 5 to 10 mM) of the extracellular K+ concentration. They suggest that only VRA seem suited to uptake of extracellular K+ via IKin channels at physiological membrane potential. The expression of Kir4.1 in a limited population of astrocytes in our study might correspond to their classification of astrocytes.
In this study, we further showed that in the olfactory bulb the
reciprocal synapses are more frequently surrounded by astrocyte processes expressing Kir4.1 than the excitatory synapses. This suggests
that some specific signals from synapses may induce expression and
control of subcellular localization of Kir4.1 in astrocyte processes.
In the olfactory bulb, several studies have indicated that glutamate is
the neurotransmitter at the olfactory nerve excitatory synapses, while
both glutamate and -aminobutyric acid (GABA) are released at the
reciprocal synapses between mitral and periglomerular cells in
glomeruli, and also at those between mitral and granule cells in the
external plexiform layer (33). Matsutani and Yamamoto
(22) showed, in coculture of astrocytes and neurons, that
GABA released from neurons induces morphological alterations of
astrocytes via activation of GABAA receptors. Therefore, GABA released at the reciprocal synapses might be involved in the
preferential distributions of Kir4.1 at the astrocytic processes surrounding reciprocal synapses in the olfactory bulb. However, because
the difference in the distribution of Kir4.1 between excitatory and
inhibitory synapses was not obvious in the cerebral cortex, hippocampus, and cerebellum (data not shown), GABA released at inhibitory synapses cannot be exclusively responsible for the differential expression of Kir4.1 at various astrocytic processes. The
expression of Kir4.1 was shown to be induced after birth in inner ear
(11, 12), in retina (15), in kidney
(unpublished observation), and also in brain (unpublished
observation). These suggest that functional activity of each tissue,
which develops after birth, may provide divergent unidentified signals
to control expression and distribution of Kir4.1 channels in the
epithelial and glial cells (17, 32). Further studies are
needed to clarify the signals and mechanisms for heterogeneous
expression and distribution of the Kir channels in various tissues,
including brain astrocytes.
Recently, Hinterkeuser et al. (14) reported that an inwardly rectifying K+ current is reduced in the astrocytes obtained from the hippocampus of Ammon's horn sclerosis (AHS) patients. They also reported that the Kir4.1 protein was detected in Ammon's horn astrocytes by immunohistochemistry (35). Therefore, possible impairment of K+ buffering by Kir4.1 in Ammon's horn might be involved in the pathogenesis of temporal lobe epilepsy in AHS patients. Thus the heterogeneity of K+ channels involved in the K+-buffering action of glial cells might play differential roles in various pathophysiological conditions of the brain. Further studies are needed to clarify the molecular bases such as K+ channels other than Kir4.1 and K+ transporters for respective properties and functions of astrocytes in various regions of the brain.
![]() |
ACKNOWLEDGEMENTS |
---|
The authors thank Dr. I. Findlay (Tours University, Tours, France) for critical reading of this manuscript, K. Takahashi and M. Fukui for technical assistance, and K. Tsuji for secretarial work.
![]() |
FOOTNOTES |
---|
This work was supported by grants to Y. Kurachi from the Ministry of Education, Science, Sports, and Culture of Japan for Grant-in-Aid for Scientific Research on Priority Area B; from the Research for the Future Program of the Japan Society for the Promotion of Science (96L00302); and from the Human Frontier Science Program (RG0158/1997-B).
Address for reprint requests and other correspondence: Y. Kurachi, Dept. of Pharmacology II, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (E-mail: ykurachi{at}pharma2.med.osaka-u.ac.jp).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 25 December 2000; accepted in final form 23 April 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Bailey, MS,
and
Shipley MT.
Astrocyte subtypes in the rat olfactory bulb: morphological heterogeneity and differential laminar distribution.
J Comp Neurol
328:
501-526,
1993[ISI][Medline].
2.
Barres, BA,
Koroshetz WJ,
Chun LL,
and
Corey DP.
Ion channel expression by white matter glia: the type-1 astrocyte.
Neuron
5:
527-544,
1990[ISI][Medline].
3.
Barres, BA,
Koroshetz WJ,
Swartz KJ,
Chun LL,
and
Corey DP.
Ion channel expression by white matter glia: the O-2A glial progenitor cell.
Neuron
4:
507-524,
1990[ISI][Medline].
4.
Bignami, A.
Neuron-Glia Interrelations During Phylogeny. I. Phylogeny and Ontogeny of Glial Cells. New Jersey: Humana, 1995, p. 3-39.
5.
Bond, CT,
Pessia M,
Xia XM,
Lagrutta A,
Kavanaugh MP,
and
Adelman JP.
Cloning and expression of a family of inward rectifier potassium channels.
Receptors Channels
2:
183-191,
1994[ISI][Medline].
6.
Brew, H,
Gray PT,
Mobbs P,
and
Attwell D.
Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering.
Nature
324:
466-468,
1986[ISI][Medline].
7.
Brismar, T,
and
Collins VP.
Inward rectifying potassium channels in human malignant glioma cells.
Brain Res
480:
249-258,
1989[ISI][Medline].
8.
D'Ambrosio, R,
Wenzel J,
Schwartzkroin PA,
Mckhann GM,
and
Janigro D.
Functional specialization and topographic segregation of hippocampal astrocytes.
J Neurosci
18:
4425-4438,
1998
9.
Derst, C,
Wischmeyer E,
Preisiq-Müller R,
Spauschus A,
Konrad M,
Hensen P,
Jeck N,
Seyberth HW,
Daut J,
and
Karshin A.
A hyperprostaglandin E syndrome mutation in Kir1.1 (renal outer medullary potassium) channels reveals a crucial residue for channel function in Kir1.3 channels.
J Biol Chem
273:
23884-23891,
1998
10.
Gosset, P,
Ghezala GA,
Korn B,
Yaspo ML,
Potska A,
Lehrach H,
Sinet PM,
and
Creau N.
A new inward rectifier potassium channel gene (KCNJ15) localized on chromosome 21 in the Down syndrome chromosome region 1 (DCR1).
Genomics
44:
237-241,
1997[ISI][Medline].
11.
Hibino, H,
Horio Y,
Fujita A,
Inanobe A,
Doi K,
Gotow T,
Uchiyama Y,
Kubo T,
and
Kurachi Y.
Expression of an inwardly rectifying K+ channel, Kir4.1, in satellite cells of rat cochlear ganglia.
Am J Physiol Cell Physiol
277:
C638-C644,
1999
12.
Hibino, H,
Horio Y,
Inanobe A,
Doi K,
Ito M,
Yamada M,
Gotow T,
Uchiyama Y,
Kawamura M,
Kubo T,
and
Kurachi Y.
An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4.1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endo-cochlear potential.
J Neurosci
17:
4711-4721,
1997
13.
Hinds, JW.
Reciprocal and serial dendrodendritic synapses in the glomerular layer of the rat olfactory bulb.
Brain Res
17:
530-534,
1970[ISI][Medline].
14.
Hinterkeuser, S,
Schröder W,
Hager G,
Seifert G,
Blümcke I,
Elger CE,
Schramm J,
and
Steinhäuser C.
Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances.
Eur J Neurosci
12:
2087-2096,
2000[ISI][Medline].
15.
Ishii, M,
Horio Y,
Tada Y,
Hibino H,
Inanobe A,
Ito M,
Yamada M,
Gotow T,
Uchiyama Y,
and
Kurachi Y.
Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Müller cell membrane: the regulation by insulin and laminin signals.
J Neurosci
17:
7725-7735,
1997
16.
Ito, M,
Inanobe A,
Horio Y,
Hibino H,
Isomoto S,
Ito H,
Mori K,
Tonosaki A,
Tomoike H,
and
Kurachi Y.
Immunolocalization of an inwardly rectifying K+ channel, KAB-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia.
FEBS Lett
388:
11-15,
1996[ISI][Medline].
17.
Kressin, K,
Kuprijanova E,
Jabs R,
Seifert G,
and
Steinhäuser C.
Developmental regulation of Na+ and K+ conductances in glial cells of mouse hippocampal brain slices.
Glia
15:
173-187,
1995[ISI][Medline].
18.
Kubo, Y,
Miyashita T,
and
Kubokawa K.
A weakly inward rectifying potassium channel of the salmon brain: glutamate 179 in the second transmembrane domain is insufficient for strong rectification.
J Biol Chem
271:
15729-15735,
1996
19.
Kuffler, SW,
Nicholls JG,
and
Orkand RK.
Physiological properties of glial cells in the central nervous system of amphibia.
J Neurophysiol
29:
768-787,
1966
20.
Kusaka, S,
Horio Y,
Fujita A,
Matsushita K,
Inanobe A,
Gotow T,
Uchiyama Y,
Tano Y,
and
Kurachi Y.
Expression and polarized distribution of an inwardly rectifying K+ channel, Kir4.1, in rat retinal pigment epithelium.
J Physiol (Lond)
520:
373-381,
1999
21.
Kusaka, S,
and
Puro DG.
Intracellular ATP activates inwardly rectifying K+ channels in human and monkey retinal Müller (glial) cells.
J Physiol (Lond)
500:
593-604,
1997[Abstract].
22.
Matsutani, S,
and
Yamamoto N.
Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling.
Glia
20:
1-9,
1997[ISI][Medline].
23.
McKhann, GM,
D'Ambrosio R,
and
Janigro D.
Heterogeneity of astrocyte resting membrane potentials and intercellular coupling revealed by whole-cell and gramicidin-perforated patch recordings from cultured neocortical and hippocampal slice astrocytes.
J Neurosci
17:
6850-6863,
1997
24.
McLarnon, JG,
and
Kim SU.
Existence of inward potassium currents in adult human oligodendrocytes.
Neurosci Lett
101:
107-112,
1989[ISI][Medline].
25.
Moliner, RE.
The reciprocal synapses of the olfactory bulb: questioning the evidence.
Brain Res
128:
1-20,
1977[ISI][Medline].
26.
Nagelhus, EA,
Horio Y,
Inanobe A,
Fujita A,
Haug FM,
Nielsen S,
Kurachi Y,
and
Ottersen OP.
Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains.
Glia
26:
47-54,
1999[ISI][Medline].
27.
Newman, EA.
Regional specialization of retinal glial cell membrane.
Nature
309:
155-157,
1984[ISI][Medline].
28.
Newman, EA.
Inward-rectifying potassium channels in retinal glial (Müller) cells.
J Neurosci
13:
3333-3345,
1993[Abstract].
29.
Orkand, RK,
Nicholls JG,
and
Kuffler SW.
Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia.
J Neurophysiol
29:
788-806,
1966
30.
Pinching, AJ,
and
Powell TPS
The neuron types of the glomerular layer of the olfactory bulb.
J Cell Sci
9:
305-345,
1971[ISI][Medline].
31.
Poopalasundaram, S,
Knott C,
Shamotienko OG,
Foran PG,
Dolly JO,
Ghiani CA,
Gallo V,
and
Wilkin GP.
Glial heterogeneity in expression of the inwardly rectifying K+ channel, Kir4.1, in adult rat CNS.
Glia
30:
362-372,
2000[ISI][Medline].
32.
Schröder, W,
Hager G,
Kouprijanova E,
Weber M,
Schmitt AB,
Seifert G,
and
Steinhäuser C.
Lesion-induced changes of electrophysiological properties in astrocytes of the rat dentate gyrus.
Glia
28:
166-174,
1999[ISI][Medline].
33.
Shepherd, GM,
and
Greer CA.
The Synaptic Organization of the Brain. New York: Oxford University Press, 1998, p. 159-203.
34.
Shuck, EM,
Piser TM,
Bock JH,
Slightom JL,
Lee KS,
and
Bienkowski JB.
Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3).
J Biol Chem
272:
586-593,
1997
35.
Steinhäuser C, Schröder W, Hinterkeuser S, Knott C, Wilkin
GP, Thomzig A, Veh RW, and Seifert G. Inward rectifier
K+ currents in hippocampal astrocytes of patients with
temporal lobe epilepsy are mediated by Kir4.1 and Kir6/SUR channels
(Abstract). Soc Neurosci Abstr 26: 1837, 2000.
36.
Takumi, T,
Isii T,
Horio Y,
Morishige K,
Takahashi N,
Yamada M,
Yamashita T,
Kiyama H,
Sohmiya K,
Nakanishi S,
and
Kurachi Y.
A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells.
J Biol Chem
270:
16339-16346,
1995
37.
Tas, PW,
Massa PT,
Kress HG,
and
Koschel K.
Characterization of a Na+/K+/Cl co-transport in primary cultures of rat astrocytes.
Biochim Biophys Acta
903:
411-416,
1987[ISI][Medline].
38.
Toida, K,
Kosaka K,
Heizmann CW,
and
Kosaka T.
Synaptic contacts between mitral/tufted cells and GABAergic neurons containing calcium-binding protein parvalbumin in the rat olfactory bulb, with special reference to reciprocal synapses between them.
Brain Res
650:
347-352,
1994[ISI][Medline].
39.
Toida, K,
Kosaka K,
Heizmann CW,
and
Kosaka T.
Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb: III. Structural features of calbindin D28K-immunoreactive neurons.
J Comp Neurol
392:
179-198,
1998[ISI][Medline].
40.
Valverde, F,
and
Lopez-Mascaraque L.
Neuroglial arrangements in the olfactory glomeruli of the hedgehog.
J Comp Neurol
307:
658-674,
1991[ISI][Medline].
41.
Zhou, M,
and
Kimelberg HK.
Freshly isolated astrocytes from rat hippocampus show two distinct current patterns and different [K+]o uptake capabilities.
J Neurophysiol
84:
2746-2757,
2000