AI Article Synopsis
- In rat brain slices, the Kv channel blocker 4-aminopyridine (4-AP) typically triggers seizure-like events, but this effect is not observed in slices from chronic epileptic rats.
- The lack of response in epileptic rats is linked to increased RNA editing of the Kv1.1 channel, specifically the Ile400Val variant (Kv1.1(I400V)), which makes these channels less sensitive to 4-AP.
- Research shows that chronic epileptic rats have significantly higher RNA editing ratios in the entorhinal cortex, which likely contributes to the decreased likelihood of 4-AP inducing seizures in these animals.
Article Abstract
In rat brain slices, the Kv channel blocker 4-aminopyridine (4-AP) induces seizure-like events. This effect is absent in slices from chronic epileptic rats generated using the kainic acid model. The reason for this phenomenon remained elusive as an altered expression level of Kv channels was ruled out as a mechanism. We recently described that the Ile400Val RNA editing of Kv1.1 generates 4-AP-insensitive Kv1 channels (Kv1.1(I400V)). We therefore hypothesized that altered RNA editing levels account for the reduced ictogenic potency of 4-AP in chronic epileptic rats. We found fourfold increased RNA editing ratios in the entorhinal cortex of chronic epileptic animals compared to healthy control animals. Electrophysiologic recordings in Xenopus oocytes revealed that the observed increased Kv1.1(I400V) editing level can in fact lead to significant loss of 4-AP sensitivity. Our data suggest that altered Kv1.1(I400V) RNA editing contributes to the reduced ictogenic potential of 4-AP in chronic epileptic rats.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1528-1167.2011.02986.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!