Change search
ReferencesLink to record
Permanent link

Direct link
KA channels suppress cellular responses to fast ripple activity – implications for epilepsy
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.ORCID iD: 0000-0003-0281-9450
2009 (English)In: BMC neuroscience (Online), ISSN 1471-2202, Vol. 10, no Suppl 1, P226- p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2009. Vol. 10, no Suppl 1, P226- p.
National Category
Neurosciences Bioinformatics (Computational Biology)
URN: urn:nbn:se:kth:diva-25916DOI: 10.1186/1471-2202-10-S1-P226OAI: diva2:360778
QC 20101104. Eighteenth Annual Computational Neuroscience Meeting: CNS*2009 Berlin, Germany. 18–23 July 2009 Available from: 2010-11-04 Created: 2010-11-04 Last updated: 2011-12-22Bibliographically approved
In thesis
1. A-type Potassium Channels in Dendritic Integration: Role in Epileptogenesis
Open this publication in new window or tab >>A-type Potassium Channels in Dendritic Integration: Role in Epileptogenesis
2009 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

During cognitive tasks, synchronicity of neural activity varies and is correlated with performance. However, there may be an upper limit to normal synchronised activity – specifically, epileptogenic activity is characterized byexcess spiking at high synchronicity. An epileptic seizure has a complicated course of events and I therefore focused on the synchronised activity preceding a seizure (fast ripples). These high frequency oscillations (200–1000 Hz) have been identified as possible signature markers of epileptogenic activity and may be involved in generating seizures. Moreover, a range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A–type potassium channel (KA). Our first objective was to investigate if KA could suppress synchronized input while minimally affecting desynchronised input. The second objective was to investigate if KA could suppress fast ripple activity. To study this I use a detailed compartmental model of a hippocampal CA1 pyramidal cell. The ion channels were described by Hodgkin–Huxley dynamics.

The result showed that KA selectively could suppress highly synchronized input. I further used two models of fast ripple input and both models showed a strong reduction in the cellular spiking activity when KA was present. In an ongoing in vitro brain slice experiment our prediction from the simulations is being tested. Preliminary results show that the cellular response was reduced by 30 % for synchronised input, thus confirming our theoretical predictions. By suppressing fast ripples KA may prevent the highly synchronised spiking activity to spread and thereby preventing the seizure. Many antiepileptic drugs down regulate cell excitability by targeting sodium channels or GABA–receptors. These antiepileptic drugs affect the cell during normal brain activity thereby causing significant side effects. KA mainly suppresses the spiking activity when the cell is exposed to abnormally high synchronised input. An enhancement in the KA current might therefore be beneficial in reducing seizures while not affecting normal brain activity.

Place, publisher, year, edition, pages
Stockholm: Universitetsservice US AB, 2009. x, 54 p.
Trita-CSC-A, ISSN 1653-5723 ; 2009:18
epileptogenesis, fast ripples, synchronicity, dendritic potentials, transient A–type potassium current, KV 4.2
National Category
Information Science
urn:nbn:se:kth:diva-11291 (URN)ISBN 978-91-7415-471-9 (ISBN)
2009-11-04, RB35, Roslagstullsbacken 35, Stockholm, 10:00 (English)
Available from: 2009-10-16 Created: 2009-10-14 Last updated: 2010-11-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Tigerholm, JennyFransén, Erik
By organisation
Computational Biology, CB
In the same journal
BMC neuroscience (Online)
NeurosciencesBioinformatics (Computational Biology)

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 30 hits
ReferencesLink to record
Permanent link

Direct link