MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

Birgit Honrath, Braxton Norwood, Gaye Tanrioever, Katarzyna Kuter, David C Henshall, Ayla Aksel-Aksoy, Gerhard Schratt, Jeroen Pasterkamp, Norbert A. Dencher, Katja Nieweg, Carsten Culmsee, Amalia Mihalea Dolga

Research output: Contribution to conferencePosterAcademic


Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in several diseases of the brain, and their activation provided neuroprotection in different paradigms of cell death, including oxidative stress and excitotoxicity.

In our study, we investigated the function and regulation of SK channel expression in different models of epilepsy and excessive neuronal firing.

As a model for hypersynchronous neuronal firing in vitro, we used primary cortical neurons either challenged with glutamate or deprived of magnesium to increase neuronal firing. In addition, we used perforant pathway stimulation (PPS) to induce hippocampal seizures in vivo. We investigated neuronal firing using multielectrode array recordings, analyze SK channel expression by Western blot, and assess mitochondrial performance by evaluating mitochondrial complex activity. MicroRNA135a-dependent effects on SK3 channels were investigated using a dual-luciferase assay.

Results and Conclusions
In vitro, analysis of neuronal firing in magnesium deprived primary neuronal cultures revealed that SK channel activation fully blocked the increase in neuronal activity, and restored homeostatic signaling. We found reduced SK3 channel expression following glutamate-induced excitotoxicity in vitro, and following PPS in the rat hippocampus in vivo. Further, PPS in vivo impaired the performance of mitochondrial complex I. Interestingly, we identified miRNA-135a as a key regulator of SK3 channel expression in primary neurons. Thus, we provide strong evidence that SK3 channels are involved in epilepsy(-like) conditions which are characterized by enhanced neuronal firing and an impairment of mitochondrial function, and the miRNA135a-dependent regulation of SK3 channel expression was unraveled as a new regulatory mechanism.
Original languageEnglish
Publication statusPublished - 2017
Event8th Annual Alliance for Healthy Aging Conference - UMCG, Groningen, Netherlands
Duration: 9-Nov-201711-Nov-2017


Conference8th Annual Alliance for Healthy Aging Conference
Internet address

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