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Ca(2+)-dependent large conductance K(+) currents in thalamocortical relay neurons of different rat strains.
MedLine Citation:
PMID:  23207578     Owner:  NLM     Status:  Publisher    
Mutations in genes coding for Ca(2+) channels were found in patients with childhood absence epilepsy (CAE) indicating a contribution of Ca(2+)-dependent mechanisms to the generation of spike-wave discharges (SWD) in humans. Since the involvement of Ca(2+) signals remains unclear, the aim of the present study was to elucidate the function of a Ca(2+)-dependent K(+) channel (BK(Ca)) under physiological conditions and in the pathophysiological state of CAE. The activation of BK(Ca) channels is dependent on both voltage and intracellular Ca(2+) concentrations. Moreover, these channels exhibit an outstandingly high level of regulatory heterogeneity that builds the basis for the influence of BK(Ca) channels on different aspects of neuronal activity. Here, we analyse the contribution of BK(Ca) channels to firing of thalamocortical relay neurons, and we test the hypothesis that BK(Ca) channel activity affects the phenotype of a genetic rat model of CAE. We found that the activation of the β(2)-adrenergic receptor/protein kinase A pathway resulted in BK(Ca) channel inhibition. Furthermore, BK(Ca) channels affect the number of action potentials fired in a burst and produced spike frequency adaptation during tonic activity. The latter result was confirmed by a computer modelling approach. We demonstrate that the β(2)-adrenergic inhibition of BK(Ca) channels prevents spike frequency adaptation and, thus, might significantly support the tonic firing mode of thalamocortical relay neurons. In addition, we show that BK(Ca) channel functioning differs in epileptic WAG/Rij and thereby likely contributes to highly synchronised, epileptic network activity.
Petra Ehling; Manuela Cerina; Patrick Meuth; Tatyana Kanyshkova; Pawan Bista; Philippe Coulon; Sven G Meuth; Hans-Christian Pape; Thomas Budde
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Pflugers Archiv : European journal of physiology     Volume:  -     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Physiology I, University of Münster, Robert-Koch-Str. 27a, Münster, Germany,
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