Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora, Luis F. Pacheco; Hernandez, Eder F.; Arshadmansab, Massoud F.; Francisco, Sebastian; Willis, Michael; Ermolinsky, Boris S.; Zarei, Masoud; Knaus, Hans‐Guenther; Garrido-Sanabria, Emilio R.

doi:10.1016/j.brainres.2008.01.017

Cited by 57 publications

(52 citation statements)

References 93 publications

(119 reference statements)

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“…The expression of a number of different K + channels, including Kv (Monaghan et al, 2008) and K Ca (BK) channels (Pacheco Otalora et al, 2008) is altered in response to pilocarpine-induced SE. The amplitude of A-type currents in the dendrites of hippocampal CA1 pyramidal neurons is reduced in response to pilocarpine-induced seizures (Bernard et al, 2004).…”

Section: Kv4 Channelepsymentioning

confidence: 99%

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

D’Adamo

Catacuzzeno

Giovanni

et al. 2013

Front. Cell. Neurosci.

105

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K+ channels are important determinants of seizure susceptibility. These membrane proteins, encoded by more than 70 genes, make the largest group of ion channels that fine-tune the electrical activity of neuronal and non-neuronal cells in the brain. Their ubiquity and extremely high genetic and functional diversity, unmatched by any other ion channel type, place K+ channels as primary targets of genetic variations or perturbations in K+-dependent homeostasis, even in the absence of a primary channel defect. It is therefore not surprising that numerous inherited or acquired K+ channels dysfunctions have been associated with several neurologic syndromes, including epilepsy, which often generate confusion in the classification of the associated diseases. Therefore, we propose to name the K+ channels defects underlying distinct epilepsies as “K+ channelepsies,” and introduce a new nomenclature (e.g., Kx.y-channelepsy), following the widely used K+ channel classification, which could be also adopted to easily identify other channelopathies involving Na+ (e.g., Navx.y-phenotype), Ca2+ (e.g., Cavx.y-phenotype), and Cl− channels. Furthermore, we discuss novel genetic defects in K+ channels and associated proteins that underlie distinct epileptic phenotypes in humans, and analyze critically the recent progress in the neurobiology of this disease that has also been provided by investigations on valuable animal models of epilepsy. The abundant and varied lines of evidence discussed here strongly foster assessments for variations in genes encoding for K+ channels and associated proteins in patients with idiopathic epilepsy, provide new avenues for future investigations, and highlight these proteins as critical pharmacological targets.

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Section: Kv4 Channelepsymentioning

confidence: 99%

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

D’Adamo

Catacuzzeno

Giovanni

et al. 2013

Front. Cell. Neurosci.

105

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“…No EM level studies have been published to define this labeling as being in axons, preterminal segments or terminals, although KCa1.1 immunolabeling is present in the active zone of glutamatergic Schaffer collateral nerve terminals located in CA1 sr (Hu et al, 2001; Sailer et al, 2006). KCa1.1 in MF axons/terminals is downregulated in the pilocarpine model of MTLE (Pacheco Otalora et al, 2008). Unlike Kv1.4 which is present in the ectopic MFs in the inner molecular layer of the dentate gyrus (Monaghan et al, 2008), the residual KCa1.1 remains in MFs within hilar and CA3 regions, and is not observed in the ectopic MFs (Pacheco Otalora et al, 2008).…”

Section: Kchs In Axons and Presynaptic Terminalsmentioning

confidence: 99%

“…KCa1.1 in MF axons/terminals is downregulated in the pilocarpine model of MTLE (Pacheco Otalora et al, 2008). Unlike Kv1.4 which is present in the ectopic MFs in the inner molecular layer of the dentate gyrus (Monaghan et al, 2008), the residual KCa1.1 remains in MFs within hilar and CA3 regions, and is not observed in the ectopic MFs (Pacheco Otalora et al, 2008). This suggests selective targeting to/retention in normal regions of MFs, and/or exclusion from ectopic regions, and presumably exacerbating the impact of MF sprouting on network hyperexcitability.…”

Section: Kchs In Axons and Presynaptic Terminalsmentioning

confidence: 99%

Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity

Trimmer

2015

Neuron

207

221

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Potassium channels (KChs) are the most diverse ion channels, in part due to extensive combinatorial assembly of a large number of principal and auxiliary subunits into an assortment of KCh complexes. This structural and functional diversity allows KChs to play diverse roles in neuronal function. Localization of KChs within specialized neuronal compartments defines their physiological role, and also fundamentally impacts their activity, due to localized exposure to diverse cellular determinants of channel function. Recent studies in mammalian brain reveal an exquisite refinement of KCh subcellular localization. This includes axonal KChs at the initial segment, and near/within nodes of Ranvier and presynaptic terminals, dendritic KChs found at sites reflecting specific synaptic input, and KChs defining novel compartments. Painting the remarkable diversity of KChs onto the complex architecture of mammalian neurons creates an elegant picture of electrical signal processing underlying the sophisticated function of individual neuronal compartments, and ultimately neurotransmission and behavior.

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“…However, the reduced BK Ca current density was not associated with downegulation of BK Ca channel α-subunit in IC neurons of GEPR-3s [96]; thus, other mechanisms (such as phosphorylation or dephosphorylation of the channel) may account for the reduced current density. In a model of TLE, however, a downregulation of the BK Ca channel α subunits was reported in the cortex and hippocampus (specifically in the mossy fibers), during the active (or chronic) phase of epilepsy [97,98]. Interestingly, BK Ca channels are abundantly expressed at glutamatergic presynaptic terminals including at the mossy fibers where they can control glutamate release under conditions of excessive neuronal activity.…”

Section: Bkca Channelsmentioning

confidence: 99%

Targeting BK (big potassium) channels in epilepsy

N’Gouemo

2011

Expert Opinion on Therapeutic Targets

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Introduction Epilepsies are disorders of neuronal excitability characterized by spontaneous and recurrent seizures. Ion channels are critical for regulating neuronal excitability and, therefore, can contribute significantly to epilepsy pathophysiology. In particular, large conductance, Ca2+-activated K+ (BKCa) channels play an important role in seizure etiology. These channels are activated by both membrane depolarization and increased intracellular Ca2+. This unique coupling of Ca2+ signaling to membrane depolarization is important in controlling neuronal hyperexcitability, as outward K+ current through BKCa channels hyperpolarizes neurons. Areas covered This review focuses on BKCa channel structure-function and discusses the role of these channels in epilepsy pathophysiology. Expert opinion Loss-of-function BKCa channels contribute neuronal hyperexcitability that can lead to temporal lobe epilepsy, tonic-clonic seizures and alcohol withdrawal seizures. Similarly, BKCa channel blockade can trigger seizures and status epilepticus. Paradoxically, some mutations in BKCa channel subunit can give rise to the channel gain-of-function that leads to development of idiopathic epilepsy (primarily absence epilepsy). Seizures themselves also enhance BKCa channel currents associated with neuronal hyperexcitability, and blocking BKCa channels suppresses generalized tonic-clonic seizures. Thus, both loss-of-function and gain-of-function BKCa channels might serve as molecular targets for drugs to suppress certain seizure phenotypes including temporal lobe seizures and absence seizures, respectively.

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Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Cited by 57 publications

References 93 publications

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity

Targeting BK (big potassium) channels in epilepsy

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