Search

Muller cells are the dominant macroglial cells in the retina of all vertebrates. They fulfill a variety of functions important for retinal physiology, among them spatial buffering of K+ ions and uptake of glutamate and other neurotransmitters. To this end, Muller cells express inwardly rectifying K+ channels and electrogenic glutamate transporters. Moreover, a lot of voltage- and ligand-gated ion channels, aquaporin water channels, and electrogenic transporters are expressed in Muller cells, some of them in a species-specific manner. For example, voltage-dependent Na+ channels are found exclusively in some but not all mammalian species. Whereas a lot of data exist from amphibians and mammals, the results from other vertebrates are sparse. It is the aim of this review to present a survey on Muller cell electrophysiology covering all classes of vertebrates. The focus is on functional studies, mainly performed using the whole-cell patch-clamp technique. However, data about the expression of membrane channels and transporters from immunohistochemistry are also included. Possible functional roles of membrane channels and transporters are discussed. Obviously, electrophysiological properties involved in the main functions of Muller cells developed early in vertebrate evolution. GLIA 2017;65:533-568.

Neocortical astrocytes make two types of gap junctions, intercellular ones create a functional syncytium, while reflexive gap junctions mediate autocellular coupling and serve unknown functions (Rohlmann and Wolff, 1996). Here, the question is addressed whether solitary astrocytes in vitro express connexin43 (Cx43) and establish gap junctions in the absence of intercellular contacts. In all media conditions tested, immunocytochemistry visualized Cx43-expression and gap junctions irrespective of the presence or absence of intercellular contacts. Reflexive gap junctions were associated with mechanical junctions (adherent spots and fascia adherens) connecting surface membranes and cytoskelal components, respectively. Both were characteristically located along incompletely separated borders between developing processes and/or branches. In addition, Cx43-immunoreactivity was found on some non-junctional membranes: i) intracellular vesicle clusters sited to forming processes and at the basis of filopodia; ii) the surface membrane of filopodial subpopulations usually appearing in bunches. Results suggest changes in the resumptive role of Cx43 in cultivated astrocytes: 1) Cx43 is not confined to intercellular gap junctions, it may even selectively compose reflexive ones; 2) from intracellular stores (vesicle aggregates), Cx43 may be incorporated into the surface membrane of filopodia; 3) by contacting other parts of the same cell surface (or neighboring cells), filopodia and membrane patches carrying Cx43-half channels may be essential in initial steps of gap junction formation; 4) the distribution of reflexive gap junctions is compatible with the hypothesis that autocellular coupling serves reorganization of cytoskeleton during the formation of cell processes and branches; 5) in general, gap junctions may be important for coordinating the cytoskeleton across intercellular contacts and within cells with complex shape.

During an entire lifetime, sensory axons of regenerating olfactory receptor neurons can enter glomeruli in the olfactory bulb and establish synaptic junctions with central neurons. The role played by astrocytes in this unique permissiveness is still unclear. Glomerular astrocytes have been identified by immunocytochemistry for glial fibrillary acidic protein and S100 proteins at the light and electron microscopic levels. The latter labeling included submicroscopic lamellar and filopodial extensions of astroglial processes. Cell bodies and processes accumulate along the border between juxtaglomerular walls and glomerular neuropil. Within glomeruli, a network of astroglial processes encloses mesh-like neuropil zones devoid of astroglia. Electron microscopy confirmed the division into subcompartments of glomerular neuropil: 1) The "sensory-synaptic subcompartment" includes all sensory axon terminals and terminal dendritic branches receiving sensory input, whereas astroglia are excluded; 2) in the "central-synaptic subcompartment," astroglial processes are intermingled with other neuropil components: dendrites of relay cells and interneurons, dendrodendritic synapses, centrifugal (cholinergic and serotonergic) axons, their axodendritic synapses, and blood vessels. Unevenly distributed astroglial processes in this subcompartment are attached to vascular basal laminae, stem dendrites, and subpopulations of dendrodendritic synapses, especially those colocalized with centrifugal projections ("triadic synapses"). Astroglia-free parts of the "central" subcompartment contain segments of dendrites and subpopulations of dendrodendritic synapses. Because of the subdivision of the glomerular neuropil into portions with and without glial components, glia do not completely demarcate the border between the "sensory" and the "central" subcompartments. Interdigitation between the subcompartments varies among glomeruli and even within a single glomerulus. The mesh width of astroglial networks covaries with numerical relations between sensory and dendrodendritic synapses. This distribution pattern of astrocytes suggests that these glial cells monitor brain-derived effects on olfactory glomerular neuropil rather than olfactory input and that astroglial processes are (re-)arranged accordingly.

Within the last few years, the expression of voltage-dependent, TTX-sensitive Na+ channels has been demonstrated in several types of neuroglial cells such as astrocytes and Schwann cells. Recently, we reported the occurrence of such Na+ currents in retinal Muller (glial) cells from dog and cat. This paper deals with the description of the properties of Na+ currents in Muller cells isolated from retinae of several mammalian species, as well as from human retinae. These Na+ currents were eliminated by TTX (1μM), and by exposure to sodium-free extracellular solution; typically, they were de-monstrable only after blocking most of the K+ conductance by Ba2+ (1 mM). Voltage-dependent activation and inactivation characteristics and time constants of the Na+ currents were similar to those of currents carried by neuronal Na+ channels. The esti-mated number of sodium channels per cell was low (about 1,500 channels per 7,500μm2), and the K+ conductance exceeded the peak Na+ conductance by an average factor of 5. Thus, the cells were incapable of generating action-potential-like responses under cur-rent clamp. Modelling estimations show that triggering of glial Na+ currents under physiological conditions, if any, can at best occur by ephaptic transmission at perinodal sites of optic axons. It is speculated that glial Na+ channels might be involved in neuro-glial signalling events. © 1994 Wiley-Liss, Inc.

The transcription factor Tieg1/Klf10 belongs to a family of Sp1/Klf proteins that have been shown to play important roles during development and maintenance of various tissues and cell types. Upregulation of Tieg1/Klf10 has been reported for TGF-beta, BMP2, BMP4, ActivinA and GDNF as members of the TGF-beta superfamily. Moreover, estrogen, the cytostatic drugs homoharringtonine and velcade as well as nitric oxide are also able to trigger Tieg1/Klf10 transcription. Recent studies suggest a role for members of the neurotrophin family in regulating Tieg1/Klf10 transcriptional upregulation. Using semi-quantitative RT-PCR and immunoblotting, we present data describing that nerve growth factor (NGF) regulates the expression of Tieg1/Klf10 in the pheochromocytoma cell line PC12 in a TrkA-dependent manner. Moreover, we provide evidence for the existence of NGF-responsive elements in the 5'-regulatory region of Tieg1/Klf10 that contain binding sites for the transcription factors Sp1 and CREB. After treatment with NGF PC12 cells exit the cell cycle and start to differentiate towards a neuron-like phenotype indicated by neurite outgrowth. Using flow cytometry and differentiation assays we demonstrate that Tieg1/Klf10 reduces cell cycle progression in PC12 cells but fails to promote their terminal differentiation. Together, our results identify Tieg1/Klf10 as a new NGF target gene and substantiate its anti-proliferative function in the NGF signaling pathway in PC12 cells.

Publisher Summary This chapter reviews that cytoarchitectonics is commonly used as a descriptor of tissue architectonics. To construct stereotaxic atlases of the central nervous system (CNS), cytoarchitectonics is focused on neurons and distribution patterns of their cell bodies. The chapter discusses that the unique complexity of cellular interactions in CNS tissue is based on the intra-epithelial association of cells, and confrontation of multiple cell types of different origin and contact relations with neurons and/or intracerebral (intra-epithelial) blood vessels. To assess the interactive potential of non-neuronal cell types, their ramified shapes have to be characterized in terms of topography of structural and molecular cell components, and their contact relations within metacellular entities and tissue compartments. The chapter reviews that by utilizing structural, morphogenetic, and topographical information including quantitative data, cell-type specific cytoarchitectonics turns out to be a valuable tool that combines tissue-related cell structures with cell-related tissue compartments. This approach is exemplified by endothelia of intracerebral blood capillaries, microglia, oligodendroglia, and ependymo-astroglia with special reference to astrocytes.

There is ample evidence that retinal radial glial (Müller) cells play a crucial role in retinal ion homeostasis. Nevertheless, data on the particular types of ion channels mediating this function are very rare and incomplete; this holds especially for mammalian Müller cells. Thus, the whole-cell variation of the patch-clamp technique was used to study voltage-dependent currents in Müller cells from adult rabbit retinae. The membrane of Müller cells was almost exclusively permeable to K+ ions, as no significant currents could be evoked in K(+)-free internal and external solutions, external Ba2+ (1 mM) reversibly blocked most membrane currents, and external Cs+ ions (5 mM) blocked all inward currents. All cells expressed inwardly rectifying channels that showed inactivation at strong hyperpolarizing voltages (or = -120 mV), and the conductance of which varied with the square root of extracellular K+ concentration ([K+]e). Most cells responded to depolarizing voltages (or = -30 mV) with slowly activating outward currents through delayed rectifier channels. These currents were reversibly blocked by external application of 4-aminopyridine (4-AP, 0.5 mM) or tetraethylammonium (TEA,20 mM). Additionally, almost all cells showed rapidly inactivating currents in response to depolarizing (or = -60 mV) voltage steps. The currents were blocked by Ba2+ (1 mM), and their amplitude increased with the [K+]e. Obviously, these currents belonged to the A-type family of K+ channels. Some of the observed types of K+ channels may contribute to retinal K+ clearance but at least some of them may also be involved in regulation of proliferative activity of the cells.