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
Episodic ataxia type 1 mutations differentially affect neuronal excitability and transmitter release.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Heeroma JH, Henneberger C, Rajakulendran S, Hanna MG, Schorge S, Kullmann DM
  • Publication date:
  • Pagination:
    612, 619
  • Journal:
    Dis Model Mech
  • Volume:
  • Issue:
  • Status:
  • Country:
  • PII:
  • Language:
  • Keywords:
    Animals, Animals, Newborn, Ataxia, Disease Models, Animal, Heterozygote, Hippocampus, Humans, Kv1.1 Potassium Channel, Lentivirus, Mutation, Neurons, Neurotransmitter Agents, Promoter Regions, Genetic, Protein Structure, Tertiary, Rats
Heterozygous mutations of KCNA1, the gene encoding potassium channel Kv1.1 subunits, cause episodic ataxia type 1 (EA1), which is characterized by paroxysmal cerebellar incoordination and interictal myokymia. Some mutations are also associated with epilepsy. Although Kv1.1-containing potassium channels play important roles in neuronal excitability and neurotransmitter release, it is not known how mutations associated with different clinical features affect the input-output relationships of individual neurons. We transduced rat hippocampal neurons, which were cultured on glial micro-islands, with lentiviruses expressing wild-type or mutant human KCNA1, and injected either depolarizing currents to evoke action potentials or depolarizing voltage commands to evoke autaptic currents. alpha-Dendrotoxin and tetraethylammonium allowed a pharmacological dissection of potassium currents underlying excitability and neurotransmission. Overexpression of wild-type Kv1.1 decreased both neuronal excitability and neurotransmitter release. By contrast, the C-terminus-truncated R417stop mutant, which is associated with severe drug-resistant EA1, had the opposite effect: increased excitability and release probability. Another mutant, T226R, which is associated with EA1 that is complicated by contractures and epilepsy, had no detectable effect on neuronal excitability; however, in common with R417stop, it markedly enhanced neurotransmitter release. The results provide direct evidence that EA1 mutations increase neurotransmitter release, and provide an insight into mechanisms underlying the phenotypic differences that are associated with different mutations.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Clinical & Experimental Epilepsy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by