Researchers discover novel mode of neurotransmitter-based communication

Indigophoton · May 21, 2018

Researchers at the University of California, Irvine School of Medicine have discovered the first example of a novel mode of neurotransmitter-based communication. The discovery, published in Nature Communications, challenges current dogma about mechanisms of signaling in the brain, and uncovers new pathways for developing therapies for disorders like epilepsy, anxiety and chronic pain.

Voltage-gated potassium channels (KCNQ2-5) generate the M-current, which helps control neuronal excitability. Subunits of these channels each have high-affinity anticonvulsant drug-binding pockets, which UCI researchers discovered accommodate endogenous neurotransmitters, including Gamma-aminobutyric acid (GABA), one of the most influential neurotransmitters in the nervous system.

The UCI research team, led by postdoctoral fellow Rían Manville, Ph.D. and principal investigator Geoffrey Abbott, MSc, Ph.D., together with postdoctoral fellow Maria Papanikolaou, MSc, Ph.D., examined an ancient sequence motif, previously identified as a drug-binding site but overlooked with respect to native function. It was there that the team discovered a binding pocket for GABA.
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"Our findings suggest the potential for an underlying feedback mechanism, as M-channels were previously found to regulate GABA release," said Abbott. "Additionally, our results demonstrate that certain KCNQ channels have the capacity to act as chemosensors of the extracellular neurotransmitter/metabolite landscape, which could enable M-channels to respond to the balance of these molecules and by doing so regulate cellular excitability over time."

KCNQ channels are present in both ancient and modern nervous systems and each responds to GABA differently. These channels are already targets for antiepileptic drugs, however, the first of these drugs was recently withdrawn due to unwanted off-target effects. With the identification of direct neurotransmitter activation of these channels, the potential for new epilepsy, anxiety and pain drugs that exploit this alternative chemical space is well within reach.

The team also found that synthetic and naturally occurring metabolites and analogs of GABA, including beta-hydroxybutyrate (BHB), also activate KCNQ channels. They are currently conducting additional studies exploring the role for BHB activation of KCNQ2/3 channels in anticonvulsant effects of the ketogenic diet, given that BHB is the first ketone body produced during fasting or ketogenic diets, and also in diabetic ketoacidosis.
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Emphasis added.

https://m.medicalxpress.com/news/2018-05-mode-neurotransmitter-based.html

JaimeS · May 21, 2018

.....I thought there were already papers on this? Is this an example of the "we've discovered a new x!" that isn't really new? Or did this get oversimplified, I wonder?

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