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.

Epilepsy is a chronic disorder in which neuronal hyperexcitability and excessive synchronization generate abnormal brain electrical activity (seizures), which can in turn produce absences, loss of consciousness, limb stiffening and/or jerking (convulsions), or atonia. Channelopathy disorders are caused by the abnormal functioning of ion channel subunits [4]. The leading sources of channel dysfunction are de novo and inherited nucleotide changes, which can be classified as gain- or loss-of-function (GOF, LOF) mutations. GOF mutations alter channel activity in a way that increases current magnitude or duration, whereas LOF produces the opposite effect, to reduce current size or duration. BK channels are large-conductance, voltage, and calcium-activated potassium channels. BK channels leads to massive efflux of K+ ions, that hyperpolarizes cellular membrane potential [17]. They conduct large amount of K ions across the cell membrane hence their name big potassium [9]. These channels are activated opened by either electrical means or by increasing calcium concentration in cell [10]. BK channels help regulate physiological processes such as neuronal excitability, smooth muscle contractility and circadian behavioral rhythms [18]. It is also involved in many processes in the body as it is a ubiquitous channel.  It has not yet been established how the genetic changes alter BK channel function and under which conditions these alterations manifest [9]

Depolarization of the membranevoltage and increased intracellular Ca2+ levels both cause BK channels to open, whichhyperpolarizes the membrane and closes voltage-dependent channels, including Ca2+channels, reducing Ca2+ influx into the cell [6]. Gating by voltage and Ca2+ confers specialized regulation of membrane potential in excitable cells. BK channels are expressed widely in neurons and muscle, where they exert specific effects on membrane potential through different splice variants, interactions with accessory subunits, and coupling to Ca2+ sources [17]This selective tuning of BK channel properties through different molecular mechanisms and protein interactions produces distinct functional consequences for excitability. In the brain, the BK channel performs dual roles in regulating excitability depending on neuronal type [9] For example, BK channel activation can either deaccelerate (Purkinje neurons) or speed (GABAergic neurons) action potential (AP) firing, and therefore modulate neurotransmitter release Latorre et al. 2017; Tseng-Crank et al. 1994). Thus BK channels manifest their pivotal role in preventing transmitter-related hyperexcitability, and therefore neuronal dysfunction, through this balance of activity.

They have tetrameric structure that is composed of a transmembrane domain voltage sensing, potassium channel and a cytoplasmic c-terminal domain.[15] Their function is repolarizing the membrane potential by allowing for potassium to flow outward response in response to depolarization or increase in Ca+2 levels (Castillo, Contreras et al. 2015).

BK channels are homologous to voltage and ligand gated K+ channelhaving a voltage sensor and pore as the membrane spanning domain in a cytosolic domain for the binding of intracellular Ca and Mg each monomer of the channel forming alpha subunit is the product is consisting of Kca1 gene also known as slo1.(Horrigan, Gonzalez et al. 2019) It has three main structural domain such as 1) the voltage sensing domain (VSD) senses membrane potential across the membrane, 2) the cytosolic domain (senses calcium concentration, Ca²⁺ ions), and 3) the pore-gate domain (PGD) which opens and closes to regulate potassium permeation. [12]

BK channels are large conductance of Ca gated and K+ channels and it consists of 4subunits and one gene encoded for this is KCa1 gene [4]. They are six transmembrane domain K+ channel has two main subunits such as: 1) Voltage gated K+ channels (Kv).  2) Calcium gated K+ channel (Kca).(Cheng, Wright et al. 2016)

The Kv has subclassified into Kv1 to Kv12 and Kv1 is subclass into Kv1.1 to Kv1.8 and are formed from the total 40 genes.(Stevens and Patel 2016)They also have intrinsic calcium binding sites in their carboxyl terminal tail that impart low affinity calcium activation. They have a potassium selectivity sequence that allows high conductance while maintaining selectivity for potassium. BK channels also assemble with a family of twotransmembrane accessory  subunits (1–4), through interactions in the N-terminus-S3 domain.[16]

From the functional point of view, all Kv channels are activated by depolarization and deactivated by repolarization, both relatively fast. Inactivation occurs when the open channel is occluded via intracellular “ball domains” during prolonged depolarization.