Fruit flies can help us for the development of improved anesthetics

20 March 2013

​General anesthetic result in a loss of consciousness and insensitivity to pain, apparently in the same manner in all animals, from invertebrates to humans. However, the molecular mechanisms involved are not yet known. Recent research by Patrik Verstreken (VIB/KU Leuven) about the role of the lipid PIP3 in brain cells of fruit flies could provide more insight into this.

Fruit flies lead the way
Brain cells communicate with each other via electrical signals that are transmitted into a chemical signal at the level of the synapse. This occurs via a vesicle or small bubble that contains neurotransmitters. When these vesicles fuse with a neuron, the neurotransmitters are released. These neurotransmitters bind to the next neuron in line, so that it becomes electrically activated. This is called neurotransmission. Verstreken’s team examines the role of proteins and other substances in the synapse and they use fruit flies for this research. The protein syntaxin has been known for some time to play an important role in this neurotransmission, also in humans. Syntaxin must accumulate – in a so-called cluster – for an optimum effect.

The VIB scientists used high resolution microscopy and new genetic tools to demonstrate that PIP3 interacts with syntaxin in the synapses. The electrostatic interactions between the negatively charged lipid PIP3 and a positively charged domain of syntaxin ensure the clustering of syntaxin at sites of neurotransmission. Investigators observed that fruit flies with too little PIP3 in the synapse exhibited poor clustering of syntaxin and decreased neurotransmission. This resulted in the fruit flies becoming intoxicated easily.

General anesthetic
Anesthetic drugs are used every day for the purpose of general anesthesia. Anesthetics work by reducing neurotransmission and they possess specific properties that caused Patrik Verstreken and his team to suspect that they interfere with the PIP3-syntaxin interaction and thereby counter neurotransmission.

Patrik Verstreken (VIB/KU Leuven): “The identification of the primary target of specific anesthetics can provide insight into how these medicines work. This is important for the development of optimized anesthetics.”
Watch the video of neurotransmission on YouTube.

Intoxicated & sober fruit flies
(c) Patrik Verstreken

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