Dataset Information

Upregulation of STREX splice variant of the large conductance Ca2+-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy.

ABSTRACT: Functional properties of large conductance Ca(2+) activated potassium (BK) channels are determined by complex alternative splicing of the Kcnma1 gene encoding the alpha pore-forming subunit. Inclusion of the STREX exon in a C-terminal splice site is dynamically regulated and confers enhanced Ca(2+) sensitivity and channel inhibition via cAMP-dependent phosphorylation. Here, we describe a real time quantitative PCR (qPCR) approach to investigate relative changes in the expression of STREX and ZERO splice variants using a newly designed set of probes and primers for TaqMan-based qPCR analysis of cDNA from the rat dentate gyrus at different time points following pilocarpine-induced status epilepticus. Reduction in Kcnma1 gene expression is associated with a relative increase of STREX splice variant. Relative expression of STREX variant mRNA was increased at 10 days and at more than 1 month following status epilepticus. The biological consequences of seizure-related changes in alternative splicing of Kcnma1 deserve additional investigation.

SUBMITTER: Ermolinsky BS

PROVIDER: S-EPMC2997846 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Upregulation of STREX splice variant of the large conductance Ca2+-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy.

Ermolinsky Boris S BS Skinner Frank F Garcia Ileana I Arshadmansab Massoud F MF Otalora Luis F Pacheco LF Zarei Masoud M MM Garrido-Sanabria Emilio R ER

Neuroscience research 20101008 1

Functional properties of large conductance Ca(2+) activated potassium (BK) channels are determined by complex alternative splicing of the Kcnma1 gene encoding the alpha pore-forming subunit. Inclusion of the STREX exon in a C-terminal splice site is dynamically regulated and confers enhanced Ca(2+) sensitivity and channel inhibition via cAMP-dependent phosphorylation. Here, we describe a real time quantitative PCR (qPCR) approach to investigate relative changes in the expression of STREX and ZER ...[more]

PMID: 20933547

Similar Datasets

Project description:OBJECTIVES:Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC). METHODS:Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density. RESULTS:The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs. CONCLUSIONS:Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment

Dataset Information

Upregulation of STREX splice variant of the large conductance Ca2+-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy.

Publications

Upregulation of STREX splice variant of the large conductance Ca2+-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets