Audiogenic kindling changes the subunit composition of BK-channels in dentate gyrus of Krushinskii-Molodkina rats

Savina, T. A.; Levin, S. G.; Полетаева, И. И.; Федотова, И. Б.; Shchipakina, T. G.

doi:10.1134/s1990747813050164

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…However, no significant change was observed in the abundance of BK Ca channel α subunit proteins in IC neurons of the GEPR (N'Gouemo et al, 2009 ). Similarly, the expression of BK Ca channel α subunit was not altered in the dentate gyrus of the Krushinskii-Molodkina rat, a model of inherited epilepsy (Savina et al, 2014 ). Nevertheless, the protein expression of BK Ca channel β 4 subunits was elevated in the dentate gyrus of the Krushinskii-Moslodkina rat (Savina et al, 2014 ).…”

Section: Bk Ca Channel Loss-of-function Hypothesismentioning

confidence: 98%

“…Similarly, the expression of BK Ca channel α subunit was not altered in the dentate gyrus of the Krushinskii-Molodkina rat, a model of inherited epilepsy (Savina et al, 2014 ). Nevertheless, the protein expression of BK Ca channel β 4 subunits was elevated in the dentate gyrus of the Krushinskii-Moslodkina rat (Savina et al, 2014 ). The upregulation of β 4 subunit is consistent with loss-of-function because this subunit inhibits BK Ca channel activity (Brenner et al, 2005 ).…”

Section: Bk Ca Channel Loss-of-function Hypothesismentioning

confidence: 98%

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BK_Cachannel dysfunction in neurological diseases

N’Gouemo

2014

Front. Physiol.

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The large conductance, Ca2+-activated K+ channels (BKCa, KCa1.1) are expressed in various brain neurons where they play important roles in regulating action potential duration, firing frequency and neurotransmitter release. Membrane potential depolarization and rising levels of intracellular Ca2+ gated BKCa channels, which in turn results in an outward K+ flux that re/hyperpolarizes the membrane. The sensitivity of BKCa channels to Ca2+ provides an important negative-feedback system for Ca2+ entry into brain neurons and suppresses repetitive firing. Thus, BKCa channel loss-of-function gives rise to neuronal hyperexcitability, which can lead to seizures. Evidence also indicates that BKCa channels can facilitate high-frequency firing (gain-of-function) in some brain neurons. Interestingly, both gain-of-function and loss-of-function mutations of genes encoding for various BKCa channel subunits have been associated with the development of neuronal excitability disorders, such as seizure disorders. The role of BKCa channels in the etiology of some neurological diseases raises the possibility that these channels can be used as molecular targets to prevent and suppress disease phenotypes.

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Section: Bk Ca Channel Loss-of-function Hypothesismentioning

confidence: 98%

Section: Bk Ca Channel Loss-of-function Hypothesismentioning

confidence: 98%

BK_Cachannel dysfunction in neurological diseases

N’Gouemo

2014

Front. Physiol.

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“…Postseizure BK channel hyperactivity could result from increased transcription and/or translation of BK α. Accordingly, in a rat model of genetic predisposition to audiogenic seizures (Krushinskii–Molodkina rats), exposure to audiogenic stimuli transiently upregulates BK α protein levels in the dentate gyrus, with a significant increase detected 3 days but not 14 days postseizure (Savinaa, Levina, Poletaevab, Fedotovab, & Shchipakinaa, 2014). Alternatively, the increase in neuronal BK currents might result from post-translational modification of existing channels.…”

Section: Role Of Bk Channels In Cns Function and Pathologiesmentioning

confidence: 99%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

136

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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“…Upregulation of BK α and downregulation of β4 protein were reported after seizure induction in rats (Savina et al, 2014), and β4 mRNA was downregulated in DG cells in the hippocampus following pilocarpine-induced seizure (Whitmire et al, 2017). BK currents in somatosensory cortex were significantly increased after picrotoxin-induced seizure in mice, and the increased neuronal firing activity was normalized with BK channel inhibitors .…”

Section: Lessons From Animal Studies Linking Changes In Bk Channel Fumentioning

confidence: 96%

KCNMA1-linked channelopathy

Bailey

Moldenhauer

Park

et al. 2019

Preprint

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KCNMA1 encodes the pore-forming α subunit of the 'Big K + ' (BK) large conductance calcium and voltage-activated K + channel. BK channels are widely distributed across tissues, including both excitable and non-excitable cells. Expression levels are highest in brain and muscle, where BK channels are critical regulators of neuronal excitability and muscle contractility. A global deletion in mouse (KCNMA1 -/-) is viable but exhibits pathophysiology in many organ systems. Yet despite the important roles in animal models, the consequences of dysfunctional BK channels in humans are not well-characterized. Here, we summarize 16 rare KCNMA1 mutations identified in 37 patients dating back to 2005, with an array of clinically defined pathological phenotypes collectively referred to as 'KCNMA1-linked channelopathy.'These mutations encompass gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity, as well as several variants of unknown significance (VUS). Human KCNMA1 mutations are primarily associated with neurological conditions, including seizures, movement disorders, developmental delay, and intellectual disability. Due to the recent identification of additional patients, the spectrum of symptoms associated with KCNMA1 mutations has expanded but remains primarily defined by brain and muscle dysfunction.Emerging evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with semi-distinct patient symptoms, such as paroxysmal nonkinesigenic dyskinesia (PNKD) with GOF and ataxia with LOF. However, due to the de novo origins for the majority of KCNMA1 mutations identified to date, and the phenotypic variability exhibited by patients, additional evidence is required to establish causality in most cases. The symptomatic picture developing from patients with KCNMA1-linked channelopathy highlights the importance of better understanding the roles BK channels play in regulating cell excitability.Establishing causality between KCNMA1-linked BK channel dysfunction and specific patient symptoms may reveal new treatment approaches with the potential to increase therapeutic efficacy over current standard regimens.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.27876v3 | CC BY 4.0 Open Access | rec

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Audiogenic kindling changes the subunit composition of BK-channels in dentate gyrus of Krushinskii-Molodkina rats

Cited by 6 publications

References 23 publications

BK_Cachannel dysfunction in neurological diseases

BK_Cachannel dysfunction in neurological diseases

BK Channels in the Central Nervous System

KCNMA1-linked channelopathy

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Audiogenic kindling changes the subunit composition of BK-channels in dentate gyrus of Krushinskii-Molodkina rats

Cited by 6 publications

References 23 publications

BKCachannel dysfunction in neurological diseases

BKCachannel dysfunction in neurological diseases

BK Channels in the Central Nervous System

KCNMA1-linked channelopathy

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BK_Cachannel dysfunction in neurological diseases

BK_Cachannel dysfunction in neurological diseases