Key result
Both up-regulation and down-regulation of BK channel activity, through gene mutations, polymorphism, or pharmacological agents, have been linked to the onset of epilepsy.
This review highlights the complex, paradoxical role of BK channels in epilepsy, where both loss- and gain-of-function alterations can increase membrane excitability and contribute to epileptogenesis.
Bidirectional BK modulation warrants caution in epilepsy therapy; leaves open optimal targeting strategies for trials.
BACKGROUND & OBJECTIVE: The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. Moreover, after-hyperpolarization induced by BK channels closes Cav channels and thus precludes excessive Ca2+ influx. Considering this negative feedback effect, BK channel seemly acts to decrease membrane excitability in order to prevent hyperexcitation which is a typical characteristic of epilepsy. Therefore, one may reasonably suppose that membrane excitability would increase when the BK channel activity decreases. However, the membrane excitability displays elevation when the function of BK channel is under either upregulated or down-regulated status. Factors altering the activity of BK channels, such as gene mutations, polymorphism, channel openers or blockers that lead to loss- or gain-of-function, have all been linked to epilepsy onset. CONCLUSION: The aim of this review is to summarize existing knowledge and recent findings on the molecular properties, signaling complex and channel dysfunction of the BK channels with a particular attention to the possible relevance to the pathophysiology of epilepsy.
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Zang et al. (2018) conducted a review in Epilepsy. BK channel activity alteration was evaluated. Both up-regulation and down-regulation of BK channel activity, through gene mutations, polymorphism, or pharmacological agents, have been linked to the onset of epilepsy.
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