Large conductance voltage-and calcium-activated K+ (BK) channel in health and disease.

Large Conductance Voltage- and Calcium-activated K+ (BK) channels are transmembrane pore-forming proteins that regulate cell excitability and are also expressed in non-excitable cells. They play a role in regulating vascular tone, neuronal excitability, neurotransmitter release, and muscle contraction. Dysfunction of the BK channel can lead to arterial hypertension, hearing disorders, epilepsy, and ataxia. Here, we provide an overview of BK channel functioning and the implications of its abnormal functioning in various diseases. Understanding the function of BK channels is crucial for comprehending the mechanisms involved in regulating vital physiological processes, both in normal and pathological conditions, controlled by BK. This understanding may lead to the development of therapeutic interventions to address BK channelopathies.

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

BK channels are large conductance potassium channels characterized by four pore-forming α subunits, often co-assembled with auxiliary ß 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.

BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey.

In the 1970s, calcium-activated potassium currents were recorded for the first time. In 10years, this Ca2+-activated potassium channel was identified in rat skeletal muscle, chromaffin cells and characterized in skeletal muscle membranes reconstituted in lipid bilayers. This calcium- and voltage-activated potassium channel, dubbed BK for "Big K" due to its large ionic conductance between 130 and 300 pS in symmetric K+. The BK channel is a tetramer where the pore-forming α subunit contains seven transmembrane segments. It has a modular architecture containing a pore domain with a highly potassium-selective filter, a voltage-sensor domain and two intracellular Ca2+ binding sites in the C-terminus. BK is found in the plasma membrane of different cell types, the inner mitochondrial membrane (mitoBK) and the nuclear envelope's outer membrane (nBK). Like BK channels in the plasma membrane (pmBK), the open probability of mitoBK and nBK channels are regulated by Ca2+ and voltage and modulated by auxiliary subunits. BK channels share common pharmacology to toxins such as iberiotoxin, charybdotoxin, paxilline, and agonists of the benzimidazole family. However, the precise role of mitoBK and nBK remains largely unknown. To date, mitoBK has been reported to play a role in protecting the heart from ischemic injury. At the same time, pharmacology suggests that nBK has a role in regulating nuclear Ca2+, membrane potential and expression of eNOS. Here, we will discuss at the biophysical level the properties and differences of mitoBK and nBK compared to those of pmBK and their pharmacology and function.