A comprehensive review of peptide toxins vs synthetic modulators of BK channels in Epilepsy

Abstract

BK channels, or voltage-gated Ca2+ channels, are essential regulators of neuronal excitability and muscular contractions, all of which are abnormal in epilepsy, a chronic neuronal disease. The form, frequency, and transmission of action potentials (APs), as well as neurotransmitter release from presynaptic terminals, are all influenced by BK channels found in the plasma membrane of neurons. Over the last two decades, several naturally occurring BK channel modulators have attracted a lot of attention. The structural and pharmacological properties of BK channel blockers are discussed in this article. The properties of various venom peptide toxins from scorpions and snakes are first identified, with a focus on their distinctive structural motifs, such as their disulfide bond formation pattern, the binding interface between the toxin and the BK channel, and the functional consequences of the toxins' blockage of BK channels. Then, several non-peptide BK channel blockers are discussed, along with their molecular formula and pharmacological impact on BK channels. The precise categorization and explanations of these BK channel blockers are hoped to provide mechanistic insights into BK channel blockade. The structures of peptide toxins and non-peptide compounds may serve as models for the development of new channel blockers, as well as aid in the optimization of lead compounds for use in neurological disorders.