Journal
BRAIN
Volume 135, Issue -, Pages 3144-3152Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/aws241
Keywords
epilepsy; channelopathy; nerve excitability; neuromyotonia; potassium channel
Categories
Funding
- UK Charities' Aid Foundation Patrick Berthoud Fellowship
- British Medical Association Vera Down Fellowship
- Brain Research Trust (UK)
- Medical Research Council (UK)
- Brain Foundation (Australia)
- Sydney Foundation for Medical Research
- National Health and Medical Research Council (Australia)
- Wellcome Trust (UK)
- Action Medical Research and the European Research Council
- MRC Centre
- NHMRC
- MRC [G0802158, G0601943, G0801316, G116/147, G0200373] Funding Source: UKRI
- Action Medical Research [1725] Funding Source: researchfish
- Medical Research Council [G0801316, G116/147, G0200373, G0601943, G0802158] Funding Source: researchfish
Ask authors/readers for more resources
Benign familial neonatal epilepsy is a neuronal channelopathy most commonly caused by mutations in KCNQ2, which encodes the K(v)7.2 subunit of the slow K+ channel. K(v)7.2 is expressed in both central and peripheral nervous systems. Seizures occur in the neonatal period, often in clusters within the first few days of life, and usually remit by 12 months of age. The mechanism of involvement of K(v)7.2 mutations in the process of seizure generation has not been established in vivo. In peripheral axons, K(v)7.2 contributes to the nodal slow K+ current. The present study aimed to determine whether axonal excitability studies could detect changes in peripheral nerve function related to dysfunction or loss of slow potassium channel activity. Nerve excitability studies were performed on eight adults with KCNQ2 mutations and a history of benign familial neonatal epilepsy, now in remission. Studies detected distinctive changes in peripheral nerve, indicating a reduction in slow K+ current. Specifically, accommodation to long-lasting depolarizing currents was reduced in mutation carriers by 24% compared with normal controls, and the threshold undershoot after 100 ms depolarizing currents was reduced by 22%. Additional changes in excitability included a reduction in the relative refractory period, an increase in superexcitability and a tendency towards reduced sub-excitability. Modelling of the nerve excitability changes suggested that peripheral nerve hyperexcitability may have been ameliorated by upregulation of other potassium channels. We conclude that subclinical dysfunction of K(v)7.2 in peripheral axons can be reliably detected non-invasively in adulthood. Related alterations in neuronal excitability may contribute to epilepsy associated with KCNQ2 mutations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available