Guo, Da and Xiang, Wei and Seebahn, Angela and Becker, Cord-Michael and Strauss, Olaf (2012) Modulation of TTX-sensitive voltage-dependent Na+ channels by beta-bungarotoxin in rat cerebellar neurons. BMC Neuroscience 13, p. 36.
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PDF - Accepted Version
The modulation of voltage-dependent Na+ channels by lipid metabolites such as arachidonic acid or eicosanoids plays a role in physiological functions as well as in degenerative diseases. So far TTX-resistant channels were found mainly to be regulated by lipid metabolites.
We investigated the lipid-dependent modulation of TTX-sensitive (TTX-s) Na+ channels using beta-bungarotoxin (beta-BuTX, 10 pM), which has an intrinsic phospholipase-A2 activity, and indomethacin (10 muM), which blocks cyclooxygenase activity in primary cerebellar neurons. To investigate TTX-s Na+ channels, whole-currents were measured under K+-free conditions and blocked by 10 nM TTX. The currents resulting from calculating the difference of currents measured in the presence and the absence of TTX were used for further analysis. Application of indomethacin mainly changed the current kinetics but has only minor effects on voltage-dependence. In contrast beta-BuTX increased the maximal current amplitude and shifted the voltage-dependent activation towards more negative potentials. The effects of beta-BuTX were blocked by indomethacin. Analysis of lipid metabolites which accumulate by treatment with beta-BuTX using MALDI-TOF MS showed an increase of cyclooxygenase reaction products in relation to arachidonic acid.
In summary, we conclude that TTX-sensitive Na+ channels can be directly modulated by cyclooxygenase reaction products leading to higher activity at less depolarized potentials and subsequent higher excitability of neurons. Since activation of cyclooxygenase is also involved in pathways leading to apoptotic cells death this could play a role in degenerative diseases of the CNS and highlights a possible protective effect of cyclooxygenase inhibition.
|Date:||29 March 2012|
|Institutions:||Medicine > Lehrstuhl für Augenheilkunde|
|Projects:||Open Access Publizieren (DFG)|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Partially|
|Deposited On:||12 Apr 2012 11:07|
|Last Modified:||21 Mar 2013 12:37|