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UCL Division of Biosciences

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Astrocytes, neurotransmitter transporters and stroke

Astrocytes have been suggested to release gliotransmitters onto neurons, thus regulating their excitability and synaptic strength (Bazargani & Attwell, 2016). We are currently investigating how a previously unstudied G protein coupled receptor on astrocytes mediates this effect (Jolly, Bazargani et al., 2017), and how amine transmitters regulate astrocyte function (Bazargani & Attwell, 2017).

Patch-clamped astrocyte, gap junctionally coupled to other nearby astrocytes

Astrocytes also play a key role in regulating the excitability of neurons, and preventing excitotoxic damage, by using transporters to control the extracellular glutamate level. We pioneered the use of patch-clamp techniques to study transporters for the main excitatory neurotransmitter glutamate (Brew & Attwell, 1987), investigating in particular the ion movements which drive glutamate transport (Barbour, Brew & Attwell, 1988, Bouvier et al., 1992; Levy et al., 1998). We have demonstrated that glutamate transporters can run backwards when ion gradients run down in conditions like stroke (Szatkowski, Barbour & Attwell, 1990; Attwell et al., 1993), releasing enough glutamate to activate receptors in nearby neurons (Billups & Attwell, 1996). Indeed, in the first 10 minutes of a stroke, reversed operation of glutamate transporters is the main mechanism by which the extracellular glutamate concentration of glutamate is raised to levels which trigger the death of neurons, leading to mental and physical impairment (Rossi, Oshima & Attwell, 2000; Szatkowski & Attwell, 1994).

Using a detector neuron (left) to sense glutamate release from a glial cell (right). From Billups & Attwell (1996).

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