Ion changes and signalling in perisynaptic glia.
ABSTRACT The maintenance of ion gradients across plasma membranes is a prerequisite for the establishment of cellular membrane potentials, electrical signalling, and metabolite transport. At active synapses, pre- and postsynaptic ion gradients are constantly challenged and used for signalling purposes. Perisynaptic glia, mainly represented by fine processes of astrocytes which get into close vicinity to neuronal synapses, are required to normalize the extracellular ionic milieu and maintain ion gradients. On the other hand, perisynaptic glia itself is activated by synaptically released transmitters binding to plasma membrane receptors and transmitter carriers, and experiences significant ion changes as well. In this review we present an overview of dynamic changes of the major ion species in astrocytes in response to neuronal, especially synaptic, activity. We will focus on calcium, sodium, and proton/hydroxyl ions that play key roles in signalling processes, and will discuss the functional consequences of the glial ion signals and homeostatic processes for synaptic transmission.
- SourceAvailable from: Bruce R Ransom[show abstract] [hide abstract]
ABSTRACT: Little is known about the expression and possible functions of unopposed gap junction hemichannels in the brain. Emerging evidence suggests that gap junction hemichannels can act as stand-alone functional channels in astrocytes. With immunocytochemistry, dye uptake, and HPLC measurements, we show that astrocytes in vitro express functional hemichannels that can mediate robust efflux of glutamate and aspartate. Functional hemichannels were confirmed by passage of extracellular lucifer yellow (LY) into astrocytes in nominal divalent cation-free solution (DCFS) and the ability to block this passage with gap junction blocking agents. Glutamate/aspartate release (or LY loading) in DCFS was blocked by multivalent cations (Ca2+, Ba2+, Sr2+, Mg2+, and La3+) and by gap junction blocking agents (carbenoxolone, octanol, heptanol, flufenamic acid, and 18alpha-glycyrrhetinic acid) with affinities close to those reported for blockade of gap junction intercellular communication. Glutamate efflux via hemichannels was also accompanied by greatly reduced glutamate uptake. Glutamate release in DCFS, however, was not significantly mediated by reversal of the glutamate transporter: release did not saturate and was not blocked by glutamate transporter blockers. Control experiments in DCFS precluded glutamate release by volume-sensitive anion channels, P2X7 purinergic receptor pores, or general purinergic receptor activation. Blocking intracellular Ca2+ mobilization by BAPTA-AM or thapsigargin did not inhibit glutamate release in DCFS. Divalent cation removal also induced glutamate release from intact CNS white matter (acutely isolated optic nerve) that was blocked by carbenoxolone, suggesting the existence of functional hemichannels in situ. Our results indicated that astrocyte hemichannels could influence CNS levels of extracellular glutamate with implications for normal and pathological brain function.Journal of Neuroscience 06/2003; 23(9):3588-96. · 6.91 Impact Factor
Article: Energy on demand.[show abstract] [hide abstract]
ABSTRACT: 3 ensembles in ~1 mm with acquisition times as short as seconds. Until recently, however, it has not been clear exactly what neuronal activity is measured in PET and fMRI experiments. The basic principle of brain imaging was formulated by Sherrington more than a century ago, when he suggested that neuronal activity and energy metabolism are tightly coupled. Indeed, PET and fMRI do not detect brain activity directly but rather measure signals that reflect brain energy consumption. How then is neuronal activity related to these measures of energy consumption? Energy is delivered to the brain by the oxidation of glucose from the blood. PET monitors changes in blood flow, glucose usage, or oxygen consumption, while fMRI signals reflect the degree of blood oxygenation and flow. Thus, the metabolic signals detected by functional brain imaging techniques bring us part way to understanding how neuronal processes such as action potentials and neurotransmitter release lead to a given brain activity and its resulting behavioral state. To make further progress, it has been essential to identify and quantitate the specific cellular and molecular mechanisms of neuronal activity that are coupled to energy metabolism. New data obtained in vitro and in vivo have identified the neurotransmitter glutamate and astrocytes, a specific type of glial cells, as pivotal elements in the stoichiometric coupling of energy-requiring neuronal activities and energy metabolism. These results have related functional imaging signals and brain energy metabolism to specific neurotransmitters and thereby suggest novel solutions to a wide range of questions about brain activity. Glutamate, by far the dominant excitatory neurotransmitter of the brain, is released by ~90% of the neurons during excitation, after which it diffuses across the synaptic cleft and is recognized by receptors on the postsynaptic neuron (see the figure). Glutamate released from neurons must rapidly be removed from the synapses to set the stage for the next transmission. This is primarily accomplished by a highly efficient uptake system in the astrocytes that surround every glutamatergic synapse (see the figure). + Glutamate is taken up by astrocytes via specific transporters that use the electrochemical gradient of Na +Science 02/1999; 283(5401):496-7. · 31.03 Impact Factor
Article: Calcium signalling in glial cells.[show abstract] [hide abstract]
ABSTRACT: Calcium signals are the universal way of glial responses to the various types of stimulation. Glial cells express numerous receptors and ion channels linked to the generation of complex cytoplasmic calcium responses. The glial calcium signals are able to propagate within glial cells and to create a spreading intercellular Ca2+ wave which allow information exchange within the glial networks. These propagating Ca2+ waves are primarily mediated by intracellular excitable media formed by intracellular calcium storage organelles. The glial calcium signals could be evoked by neuronal activity and vice versa they may initiate electrical and Ca2+ responses in adjacent neurones. Thus glial calcium signals could integrate glial and neuronal compartments being therefore involved in the information processing in the brain.Cell Calcium 01/1998; 24(5-6):405-16. · 4.33 Impact Factor