The neurobiology of glia in the context of water and ion homeostasis

doi:10.1016/j.neuroscience.2004.09.053

Neuroscience

Volume 129, Issue 4, 2004, Pages 877-896

https://doi.org/10.1016/j.neuroscience.2004.09.053 Get rights and content

Abstract

Astrocytes are highly complex cells that respond to a variety of external stimulations. One of the chief functions of astrocytes is to optimize the interstitial space for synaptic transmission by tight control of water and ionic homeostasis. Several lines of work have, over the past decade, expanded the role of astrocytes and it is now clear that astrocytes are active participants in the tri-partite synapse and modulate synaptic activity in hippocampus, cortex, and hypothalamus. Thus, the emerging concept of astrocytes includes both supportive functions as well as active modulation of neuronal output.

Glutamate plays a central role in astrocytic-neuronal interactions. This excitatory amino acid is cleared from the neuronal synapses by astrocytes via glutamate transporters, and is converted into gluatamine, which is released and in turn taken up by neurons. Furthermore, metabotropic glutamate receptor activation on astrocytes triggers via increases in cytosolic Ca²⁺ a variety of responses. For example, calcium-dependent glutamate release from the astrocytes modulates the activity of both excitatory and inhibitory synapses. In vivo studies have identified the astrocytic end-foot processes enveloping the vessel walls as the center for astrocytic Ca²⁺ signaling and it is possible that Ca²⁺ signaling events in the cellular component of the blood–brain barrier are instrumental in modulation of local blood flow as well as substrate transport.

The hormonal regulation of water and ionic homeostasis is achieved by the opposing effects of vasopressin and atrial natriuretic peptide on astroglial water and chloride uptake. In conjuncture, the brain appears to have a distinct astrocytic perivascular system, involving several potassium channels as well as aquaporin 4, a membrane water channel, which has been localized to astrocytic endfeet and mediate water fluxes within the brain.

The multitask functions of astrocytes are essential for higher brain function. One of the major challenges for future studies is to link receptor-mediated signaling events in astrocytes to their roles in metabolism, ion, and water homeostasis.

Section snippets

Glutamate uptake

l-Glutamate is the major excitatory amino acid in the brain. One of the major housekeeping tasks of astrocytes is to maintain a low concentration of extracellular glutamate (<1 μM). l-Glutamate uptake by astrocytes terminates its effects as a neurotransmitter, prevents extracellular l-glutamate levels from reaching excitotoxic levels, and acts as a metabolic substrate (Rothman and Olney, 1986; Choi, 1988; Sonnewald et al., 1997). A recent publication emphasized the importance of astrocytic

Hormonal regulation of water and ionic homeostasis in astrocytes

Centrally released neuropeptides such as vasopressin (AVP), atriopeptin (ANP), angiotensinogen (AGT) and angiotensin (Ang) II appear to regulate fluid and ionic environment and cell volume in the CNS, possibly via intrinsic osmoregulation of glial cells.

Ca²⁺ signaling in astrocytes

Calcium signaling plays a central role in cell activation. Ca²⁺ is a second messenger responsible for the regulation of a wide range of cellular processes (Berridge, 1994). Astrocytic Ca²⁺ signaling is expressed as oscillations in cytosolic Ca²⁺ concentrations ([Ca²⁺]_i) and as slowly propagating waves of [Ca²⁺]_i increments (Smith, 1994). Astrocytes display regular oscillations when activated by stimuli including hormones.

In addition to Ca²⁺ oscillations, astrocytes also actively propagate Ca²⁺

Astrocytic signaling in relation to cell volume regulation and water homeostasis

Astrocytes are highly sensitive to changes in extracellular osmolarity and are capable of exhibiting prominent swelling. Decreased external osmolarity induces transient rapid swelling in glial cells, followed by a corrective process leading to cell volume recovery (Pasantes-Morales, 1996; Pasantes-Morales et al., 2000, 2002). This is an active process accomplished by the extrusion via leak pathways, of intracellular osmolytes, mainly K⁺ and Cl⁻, and organic molecules such as pyoles, and organic

Astrocytes function as a buffer of extracellular K⁺

Glial cells are essential for the maintenance of extracellular potassium ([K⁺]_e) at a level compatible with continued neuronal function (Clausen, 1992; Ballanyi, 1995). Astrocytes are connected by an extensive network of gap junctions (Cotrina et al., 1998b) which are permeable to K⁺. Thus, astrocytes form a syncytium for rapid redistribution of K⁺ from areas with high neuronal activity. Astrocytic involvement in redistribution of K⁺ from the perineuronal to perivascular areas is primarily

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The neurobiology of glia in the context of water and ion homeostasis

Abstract

Section snippets

Glutamate uptake

Hormonal regulation of water and ionic homeostasis in astrocytes

Ca2+ signaling in astrocytes

Astrocytic signaling in relation to cell volume regulation and water homeostasis

Astrocytes function as a buffer of extracellular K+

Neuroscience

Brain Res

Peptides

Neuron

Neuroscience

Mol Cell Endocrinol

Brain Res

Neuron

Prog Neurobiol

Brain Res

Neuron

Prog Neurobiol

Prog Neurobiol

FEBS Lett

Neuroscience

Trends Neurosci

) of bulk isolated glia, perikarya and synaptosomes from rabbit brain cortex. Brain Res

Neurochem Int

Neurosci Lett

Prog Neurobiol

Prog Neurobiol

J Steroid Biochem Mol Biol

Pericytes and periendothelial cells of brain parenchyma vessels co-express aminopeptidase N, aminopeptidase A, and nestin

J Neurosci Res

An ∝-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain

Proc Natl Acad Sci USA

Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of ∝-syntrophin-null mice

Proc Natl Acad Sci USA

The molecular basis of water transport in the brain

Nat Rev

Intercellular calcium signaling mediated by point-source burst release of ATP

Proc Natl Acad Sci USA

Three distinct chloride channels control anion movements in rat parotid acinar cells

J Physiol (Lond)

Modulation of glial potassium, sodium, and chloride activities by the extracellular milieu

Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen

Am J Physiol Regul Integr Comp Physiol

Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen

Hypertension

Ion channels in vertebrate glia

Annu Rev Neurosci

Role of calmodulin and protein kinase C in astrocytic cell volume regulation

J Neurochem

The presence of voltage-gated sodium, potassium and chloride channels in rat cultured astrocytes

Proc R Soc Lond B Biol Sci

Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate

Nat Neurosci

Glutamate and GABA receptors in vertebrate glial cells

Mol Neurobiol

Effects of ethylisopropyl amiloride on intracellular pH regulation in cultured rat astrocytes

Acta Physiol Scand Suppl

Isolation of nitric oxide synthase, a calmodulin-requiring enzyme

Proc Natl Acad Sci USA

Vasopressin-induced calcium signaling in cultured hippocampal neurons

Brain Res

Intracellular pH as a regulatory signal in astrocyte metabolism

Glia

Purinergic P2Y purinergic receptors on astrocytes are directly coupled to phospholipase A2

Glia

Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat: pathways to the limbic system, medulla oblongata and spinal cord

Cell Tissue Res

Characterization of the Ca2+ responses evoked by ATP and other nucleotides in mammalian brain astrocytes

Br J Pharmacol

Effect of vasopressin on brain swelling at the cellular level: do astrocytes exhibit a furosemide-vasopressin-sensitive mechanism for volume regulation

Can J Physiol Pharmacol

Neurotransmitter-mediated signaling between axons and glial cells

Glia

Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system

Neurosci

Potassium and sodium transport and pH regulation

Can J Physiol Pharmacol

Glutamate induces calcium waves in cultured astrocytes: Long-range glial signaling

Ca²⁺ signaling in astrocytes

Astrocytes function as a buffer of extracellular K⁺

Delayed K⁺ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of ∝-syntrophin-null mice

Purinergic P_2Y purinergic receptors on astrocytes are directly coupled to phospholipase A₂

Characterization of the Ca²⁺ responses evoked by ATP and other nucleotides in mammalian brain astrocytes

Ca²⁺ and filopodal responses to glutamate in cultured astrocytes and neurons