Ca2+- and Voltage-Activated K+ (BK) Channels in the Nervous System: One Gene, a Myriad of Physiological Functions

Abstract

BK channels are large conductance potassium channels characterized by four pore-forming α subunits, often co-assembled with auxiliary β and γ subunits to regulate Ca²⁺ sensitivity, voltage dependence and gating properties. BK channels are abundantly expressed throughout the brain and in different compartments within a single neuron, including axons, synaptic terminals, dendritic arbors, and spines. Their activation produces a massive efflux of K⁺ ions that hyperpolarizes the cellular membrane. Together with their ability to detect changes in intracellular Ca²⁺ concentration, BK channels control neuronal excitability and synaptic communication through diverse mechanisms. Moreover, increasing evidence indicates that dysfunction of BK channel-mediated effects on neuronal excitability and synaptic function has been implicated in several neurological disorders, including epilepsy, fragile X syndrome, mental retardation, and autism, as well as in motor and cognitive behavior. Here, we discuss current evidence highlighting the physiological importance of this ubiquitous channel in regulating brain function and its role in the pathophysiology of different neurological disorders.

Keywords: BK channels; K+ channels; ion-channels; nervous system; neurobiology; neuronal excitability; synapsis.

Figure 1

BK Channel allosteric gating mechanism. (A) H–A allosteric model [43]. Voltage sensor (R–A), Ca²⁺ binding, and C–O transitions are defined by the equilibrium constants J, K, and L, respectively. Voltage sensors and Ca²⁺ sensors are coupled to the pore by allosteric factors D and C, respectively, and coupling between sensors is performed by E. (B) Simulated data of the Log10 of the probability of opening vs. voltage obtained using the H–A model. Notice that when all the voltage sensors are at rest the parameters L, zL, and C can be obtained.

Figure 2

Structural characteristics of the BK channel. (A) The α subunit is formed by a transmembrane domain (TMD) composed of seven α helices (S0–S7) and a large carboxy terminal (CTD) containing two regulatory potassium conductance domains. (B) The BK channel is a tetramer formed by 4 α subunits in which the CTD acquires a swapped conformation and the 4 CTDs form the gating ring. (C) Top view of the BK channel. The voltage sensor domain (VSD) and the pore domain (PD) have been colored to highlight the non-swapped configuration of the VSD and the PD.