UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
In vivo loss of slow potassium channel activity in individuals with benign familial neonatal epilepsy in remission
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Tomlinson SE, Bostock H, Grinton B, Hanna MG, Kullmann DM, Kiernan MC, Scheffer IE, Berkovic SF, Burke D
  • Publication date:
    01/01/2012
  • Pagination:
    3144, 3152
  • Journal:
    Brain
  • Volume:
    135
  • Issue:
    10
  • Status:
    Published
  • Print ISSN:
    0006-8950
Abstract
Benign familial neonatal epilepsy is a neuronal channelopathy most commonly caused by mutations in KCNQ2, which encodes the Kv7.2 subunit of the slow K+ channel. Kv7.2 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 Kv7.2 mutations in the process of seizure generation has not been established in vivo. In peripheral axons, Kv7.2 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 Kv7.2 in peripheral axons can be reliably detected non-invasively in adulthood. Related alterations in neuronal excitability may contribute to epilepsy associated with KCNQ2 mutations. © 2012 The Author.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Department of Neuromuscular Diseases
Author
Department of Neuromuscular Diseases
Author
Clinical & Experimental Epilepsy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by