Description
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 enhanced neuronal firing. In vitro, analysis of neuronal firing in a model of magnesium deprivation revealed that SK channel activation fully blocked the increase in neuronal activity and restored homeostatic signaling, as assessed using a multielectrode array. We found reduced SK3 channel expression following glutamate-induced excitotoxicity in vitro, and following perforant pathway stimulation (PPS) in the rat hippocampus in vivo. Further, PPS in vivo resulted in an impairment of mitochondrial complex I performance. Interestingly, we identified miRNA-135 as a key regulator of SK3 channel expression in primary neuronal cultures. 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 miRNA-dependent regulation of SK3 channel expression was unraveled as a new regulatory mechanism.
| Period | 2017 |
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| Event title | FIGON Dutch Medicines Days |
| Event type | Conference |
| Location | Ede, NetherlandsShow on map |