miRNA-187-3p-Mediated Regulation of the KCNK10/TREK-2 Potassium Channel in a Rat Epilepsy Model.
Regulatory RNAs play a key role in the regulation of protein expression patterns in neurological diseases. Here we studied the regulation of miRNAs in a chronic rat model of temporal lobe epilepsy. The analysis was focused on a putative link with pharmacoresponsiveness as well as the functional implications of the regulation of a selected miRNA. The findings did not reveal a difference in hippocampal miRNA expression between phenobarbital responders and nonresponders. However, when comparing rats following status epilepticus with control rats we identified 13 differentially expressed miRNAs with miRNA-187-3p being most strongly regulated. mRNAs encoding KCNK10/TREK-2 as well as DYRK2 were confirmed as targets of miRNA-187-3p. Expression of the potassium channel protein KCNK10/TREK-2 negatively correlated with hippocampal miRNA-187-3p expression and proved to be upregulated in the chronic phase of the epilepsy model. In conclusion, our data do not suggest a relevant impact of miRNA expression patterns on pharmacoresponsiveness. However, we confirmed regulation of miRNA-187-3p and demonstrated that it impacts the expression of the two-pore domain potassium channel protein KCNK10/TREK-2. Considering evidence from brain ischemia models, KCNK10/TREK-2 upregulation might serve a protective function with a beneficial impact on astrocytic potassium and glutamate homeostasis.
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein , 24105 Campus Kiel, Germany.
Sierk
S
Haenisch
Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU) , 80539 Munich, Germany.
Eva-Lotta
EL
von Rüden
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein , 24105 Campus Kiel, Germany.
Hannes
H
Wahmkow
Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU) , 80539 Munich, Germany.
Maruja L
ML
Rettenbeck
Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU) , 80539 Munich, Germany.
Christina
C
Michler
Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU) , 80539 Munich, Germany.
Vera
V
Russmann
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein , 24105 Campus Kiel, Germany.
Henrike
H
Bruckmueller
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein , 24105 Campus Kiel, Germany.
Vicki
V
Waetzig
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein , 24105 Campus Kiel, Germany.
Ingolf
I
Cascorbi
Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU) , 80539 Munich, Germany.
Heidrun
H
Potschka
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy / Q000378:metabolism; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D056945:Hep G2 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D058542:Implantable Neurostimulators; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010634:Phenobarbital / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy / Q000378:metabolism; D000097603:Dyrk Kinases
D000927:Anticonvulsants; D035683:MicroRNAs; D010634:Phenobarbital; D024683:Potassium Channels, Tandem Pore Domain; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C503444:Kcnk10 protein, rat; C000611991:MIRN187 microRNA, rat
DYRK2; TREK-2; glia; glutamate; pharmacoresistant epilepsy; potassium channel