Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage-gated Ca2+ currents in Helix serotonergic neurons

Brenes, Oscar; Vandael, David; Carbone, Emilio; Montarolo, Pier Giorgio; Ghirardi, Mirella

doi:10.1016/j.neuroscience.2015.10.046

Cited by 12 publications

(4 citation statements)

References 76 publications

(105 reference statements)

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“…Furthermore, in neocortical pyramidal neurons primed by seizure activity, increased BK current amplitude is linked to both single-cell and network hyperexcitability, and the elevated firing output of postseizure neurons can be normalized by application of the BK channel blocker paxilline (Shruti et al, 2008). In snail serotonergic neurons, silencing synapsin expression also increases intrinsic excitability while concomitantly increasing the magnitude of BK currents (Brenes, Vandael, Carbone, Montarolo, & Ghirardi, 2015). Paxilline reduces firing frequency down to control levels in this system as well, further buttressing the idea that excessive BK channel activity can generate neuronal hyperexcitability.…”

Section: Role Of Bk Channels In Cns Cellular Physiologymentioning

confidence: 99%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

135

170

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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.

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Section: Role Of Bk Channels In Cns Cellular Physiologymentioning

confidence: 99%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

135

170

View full text Add to dashboard Cite

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“…20 Moreover, changes in BK channel functions can alter neuronal excitability. Genes encoding BK channels have two mutation types, namely, gain of function [20][21][22] and loss of function. [23][24][25] Both types may increase neuronal excitability.…”

mentioning

confidence: 99%

The absence of NIPA2 enhances neural excitability through BK (big potassium) channels

et al. 2019

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Summary Aim To reveal the pathogenesis and find the precision treatment for the childhood absence epilepsy (CAE) patients with NIPA2 mutations. Methods We performed whole‐cell patch‐clamp recordings to measure the electrophysiological properties of layer V neocortical somatosensory pyramidal neurons in wild‐type (WT) and NIPA2 ‐knockout mice. Results We identified that layer V neocortical somatosensory pyramidal neurons isolated from the NIPA2 ‐knockout mice displayed higher frequency of spontaneous and evoked action potential, broader half‐width of evoked action potential, and smaller currents of BK channels than those from the WT mice. NS11021, a specific BK channel opener, reduced neuronal excitability in the NIPA2 ‐knockout mice. Paxilline, a selective BK channel blocker, treated WT neurons and could simulate the situation of NIPA2 ‐knockout group, thereby suggesting that the absence of NIPA2 enhanced the excitability of neocortical somatosensory pyramidal neurons by decreasing the currents of BK channels. Zonisamide, an anti‐epilepsy drug, reduced action potential firing in NIPA2 ‐knockout mice through increasing BK channel currents. Conclusion The results indicate that the absence of NIPA2 enhances neural excitability through BK channels. Zonisamide is probably a potential treatment for NIPA2 mutation‐induced epilepsy, which may provide a basis for the development of new treatment strategies for epilepsy.

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“…BK channels regulate synaptic transmission: BK channels also appear to be essential regulators of neurotransmitter release when expressed at synaptic terminals within different brain circuits [ 14 , 16 ]. Their localization in the active zone appears to be regulated by different synaptic proteins, including RIM-binding proteins [ 189 ], synapsin [ 190 ], α-catulin [ 191 ], and dystrobrevin [ 191 , 192 ]. In the brain, the function of presynaptic BK channels in regulating neurotransmitter release may vary from synapse to synapse [ 23 , 24 ].…”

Section: Bk Channels Differentially Contribute To Control Of Brain Fu...mentioning

confidence: 99%

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

Ancatén-González

Segura

Alvarado-Sánchez

et al. 2023

IJMS

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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.

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Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage-gated Ca2+ currents in Helix serotonergic neurons

Cited by 12 publications

References 76 publications

BK Channels in the Central Nervous System

BK Channels in the Central Nervous System

The absence of NIPA2 enhances neural excitability through BK (big potassium) channels

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

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