BK Channels in the Central Nervous System

Abstract

Large conductance Ca2+- and voltage-activated K+ (BK) channels are widely distributed in the postnatal central nervous system (CNS). BK channels play a pleiotropic role in regulating the activity of brain and spinal cord neural circuits by providing a negative feedback mechanism for local increases in intracellular Ca2+ concentrations. In neurons, they regulate the timing and duration of K+ influx such that they can either increase or decrease firing depending on the cellular context, and they can suppress neurotransmitter release from presynaptic terminals. In addition, BK channels located in astrocytes and arterial myocytes modulate cerebral blood flow. Not surprisingly, both loss and gain of BK channel function have been associated with CNS disorders such as epilepsy, ataxia, mental retardation, and chronic pain. On the other hand, the neuroprotective role played by BK channels in a number of pathological situations could potentially be leveraged to correct neurological dysfunction.

RIM ‐binding proteins recruit BK‐channels to presynaptic release sites adjacent to voltage‐gated Ca 2+ ‐channels

“…Several mechanisms control the size and duration of the Ca 2+ -signals at the active zone, thereby generating temporally restricted micro-and nano-domains of Ca 2+ that determine the extent of release (e.g., see Fedchyshyn & Wang, 2005;Bucurenciu et al, 2008;Vyleta & Jonas, 2014). Among the most important of these mechanisms is the control of the AP duration by BK-channels (Fakler & Adelman, 2008;Contet et al, 2016;Griguoli et al, 2016). BK-channels are Ca 2+ -activated large-conductance K +channels that limit the duration of an AP, thereby controlling the extent of Ca 2+ -channel opening and of neurotransmitter release per AP.…”

ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis

“…AMG44 also normalized BK channel physiology in dissociated DRGs from EAE mice as well as mRNA levels of the β 4 and β 1 auxiliary subunits of BK channels ( Fig. 9, 10 (53). To this effect, a reduction in BK channel current in the DRG is also associated with nerve injury (54,55) and inflammation-induced pain (56)(57)(58).…”

Total flavones of Rhododendron simsii Planch flower protect rat hippocampal neuron from hypoxia-reoxygenation injury via activation of BKCa channel

“…BK Ca channels play an important role in regulation of neuronal function . In neurons, the BK Ca channel colocalizes with voltage‐gated calcium channel and controls the cellular activity via negative feedback regulation of Ca 2+ influx . Activation of BK Ca channel leads to cellular membrane hyperpolarization and subsequent inhibition on voltage‐gated calcium channel opening and excessive Ca 2+ influx .…”

“…[15] In neurons, the BK Ca channel colocalizes with voltage-gated calcium channel [25] and controls the cellular activity via negative feedback regulation of Ca 2+ influx. [26] Activation of BK Ca channel leads to cellular membrane hyperpolarization and subsequent inhibition on voltage-gated calcium channel opening and excessive Ca 2+ influx. [27] It was found that administration of BMS-204352, a BK Ca channel opener significantly decreased cortical infarct volume in rats subjected to middle cerebral artery occlusion.…”