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Comment by mikewarot | Hacker News Reader

>They were able to obtain brain tissue from 10 mammalian species: Etruscan shrews (one of the smallest known mammals), gerbils, mice, rats, Guinea pigs, ferrets, rabbits, marmosets, and macaques, as well as human tissue removed from patients with epilepsy during brain surgery.

Offbeat question: Could it be that epilepsy is a disorder caused by this missing ion channel, and this isn't true for all humans?

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If true, that would be an embarrassing oversight in the study as well as possibly #1 in one of those "Top 10 accidental scientific discoveries that changed everything" articles.

It is an oversight unless they identify it as a limitation in the study.

> To limit the potential confound of disease states associated with our human brain samples, we compared the biophysical properties of neurons from patients with hippocampal sclerosis; tumour; and other conditions, including gliosis and trauma. We found no significant differences in somatic outside-out currents between the three groups (Extended Data Fig. 7). We also directly tested the effect of epileptic seizures on somatic ionic conductance in rats and found no significant differences (Extended Data Fig. 7). Together, these results suggest that disease aetiology is unlikely to underlie the distinct features of human L5 neurons such as their low conductance.

Epilepsy is a really wide range of disorders with many causes that simply manifest in similar ways.

So it is possible this is a cause of a single type of epilepsy, but not all.

My own epilepsy was the result of spinal damage as a teen that left me temporarily, partially paralyzed. I regained movement but have frequent seizures from the damage.

Similarly a friend had a growth on his brain. Surgery removed it but he was epileptic for about a year after.

Disclaimer: I have not read this article. However, there are multiple known genetic epilepsy disorders that have specific ion channels that are either missing/mutated.

Maybe not missing ion channels, but it does seem to be caused by over sensitive ion channels, and several different ones. They used to think it was just sodium channels but now they find the calcium channels (which are also implicated in Bipolar Disorder) and the potassium channels can play a role.

https://www.intechopen.com/chapters/65083

They use sodium channel blocker's as both anti-epileptics and mood stabilizers.

I have Bipolar Disorders and have the CACNA1C, SCN2A, and KCNQ1 risk alleles for the disorder. Depakote used to work well for me, Lamictal worked even better, but Benzodiazepines as needed seem to help me the most. They are all used to treat epilepsy as well.

This study does not report that that layer V cortical neurons are missing a particular ion channel. They examine currents through HCN and voltaged-gated potassium channels and find differences in the total current carried that depends on species.

In general, epileptic disorders are observed across species. It's common in dogs, for instance: https://www.akcchf.org/canine-health/top-health-concerns/epi...

A ton of papers examining ion channel expression in epilepsy that should be more relevant: https://pubmed.ncbi.nlm.nih.gov/?term=human+ion+channel+epil...

Or the ion channel deficit was a side-effect of anti-seizure drugs often given to people with epilepsy, or a side-effect of having seizures, or ...

Presumably there is some "gotta be ultra-fresh" reason why they aren't taking just tissue from cadavers donated to medical schools. But this study sounds like it was pretty crappy science, even before the MIT press office folks got hold of it.

I think it should be obvious that you cannot study electrical excitability in dead, fixed cadaver tissue.

This is top-notch science, but might be hard for people to appreciate.

It's not clear that every case of epilepsy has a common cause, but this is certainly possible.

I wondered the same thing.

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