Type

Journal Article

Authors

Gary J Bassell
David C Henshall
Steve C Danzer
Raymund Y K Pun
Lindsay M Schroeder
Eva M Jimenez-Mateos
Kristen T Thomas
Scott W Danielson
Shane Rowley
Lei Xing
and 4 others

Subjects

Biochemistry

Topics
protein expression neuronal activity channel status epilepticus microrna mice knockout potassium kainic acid

MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset. (2016)

Abstract Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4.2 protein. We show that the microRNA miR-324-5p inhibits Kv4.2 protein expression and that antagonizing miR-324-5p is neuroprotective and seizure suppressive. MiR-324-5p inhibition also blocks kainic-acid-induced reduction of Kv4.2 protein in vitro and in vivo and delays kainic-acid-induced seizure onset in wild-type but not in Kcnd2 knockout mice. These results reveal an important role for miR-324-5p-mediated silencing of Kv4.2 in seizure onset.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Gary J Bassell, David C Henshall, Steve C Danzer, Raymund Y K Pun, Lindsay M Schroeder, Eva M Jimenez-Mateos, Kristen T Thomas, Scott W Danielson, Shane Rowley, Lei Xing and 4 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55