Tree resin blocks K-channels to treat neurology conditions

By Fiona BARRY

- Last updated on GMT

Synthetic versions of the acids in conifer resins can block ion channels
Synthetic versions of the acids in conifer resins can block ion channels
Resin from conifer trees hold the key to future epilepsy APIs, according to Swedish scientists.

Researchers from Linköping University say they studied 71 resin acids and found twelve which act on potassium channels, “where they keep the door open via an electrostatic mechanism, thereby curbing the harmful nerve activity.​”

"Our goal is to develop some of the most potent substances into medicines,​" said Fredrik Elinder, professor of molecular neurobiology and author of the study published in the Nature ​journal Scientific Reports​.

Ion channels

Elinder is an expert on the ion channels – the pores in the cell membrane through which charged ions can travel, making nerve and cardiac cells electrically excitable. Epilepsy, cardiac arrhythmia and chronic pain are caused by the excitability of nerve or cardiac cells being far too high.

Current epilepsy therapies work by blocking sodium ion channels, but many patients respond poorly and suffer side effects.

The sticky resins in this study instead work on potassium ion channels, suppressing the neuronal excitement that can lead to mutations and disease. Resin acids found naturally in confiers are fat-soluble and electrically charged and can therefore bind to and pull what the researchers call the ion channels' "doorknobs​".

Synthesised version ‘240’ times better

The Linköping scientists synthesised 71 new molecules based on dehydroabietic acid (DHAA), which were then tested on a hypersensitive potassium channel that was expressed in frog eggs and later in mice nerve cells.

"Twelve of the molecules were more potent than anything we'd looked at earlier,​" said PhD student Nina Ottosson, who designed the test channel and measured the electrical currents that open and close the door to the ion channel.

The most potent compound, was found to be 240 times more efficient than DHAA in opening a potassium channel.

The Swedish team has submitted patent applications for their discoveries.

Source: ​Ottosson, N. E. et al.,​ “Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability”, Sci. Rep.5​, 13278;

Doi:​ 10.1038/srep13278 (2015).

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