BK Channels: Regulation of Expression and Physiological Impact

Kundu, S. S.; Alioua, Abderrahmane; Kumar, Yogesh; Lü, Rong; Ou, Jimmy; Sánchez‐Pastor, Enrique; Li, Min; Stefani, Enrico; Toro, Ligia

doi:10.1002/9780470429907.ch12

Cited by 2 publications

(3 citation statements)

References 121 publications

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“…Depending on their localization and functional or physical association with other proteins in different neuronal cells, MaxiK channels are known to play complex roles in neuronal excitability as they can regulate high frequency firing, as well as the differential release of excitatory and non-excitatory neurotransmitters (Knaus et al, 1996, Faber and Sah, 2003, Lu et al, 2006, Kundu et al, 2009, Martire et al, 2010, Toro et al, 2014, Deng and Klyachko, 2015). In our studies, we have found several proteins involved in neuronal signaling that associate with MaxiK such as dopamine- and cAMP-regulated neuronal phosphoprotein (DARP-32), potassium voltage-gated channel subfamily KQT member 3, synaptosomal-associated protein 25, synaptic vesicle glycoprotein 2B, synaptotagmin-2, synapsin-2, neural cell adhesion molecule 1 and 2, and vesicular glutamate transporter 1 (supplementary table 2 and supplementary table 3).…”

Section: Discussionmentioning

confidence: 99%

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain

Singh

Hall

et al. 2016

Neuroscience

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Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca2+. In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit IgG and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1−/−), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In HEK293T cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ~0.6 and ~0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (~0.6) and slightly higher for HSP60 (~0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish the localization of MaxiK channel in the mouse brain mitochondria and demonstrate the interaction of MaxiK channel with GAT3 and HSP60 in neurons. The interaction of MaxiK channel with GAT3 opens the possibility of a role of MaxiK channel in GABA homeostasis and signaling.

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Section: Discussionmentioning

confidence: 99%

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain

Singh

Hall

et al. 2016

Neuroscience

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“…Perhaps other proteins can exert such an effect upon the BK channels that lead the BK channels astray when applied to glioma patients. Proteomic studies done with normal tissue indicate many proteins can physically associate with BK channels [18,212–214]. These techniques include co-immunoprecipitation, yeast two-hybrid system, fluorescence resonance energy transfer (FRET), co-localization studies using confocal microscopy.…”

Section: Proteins That Can Associate With Bk Channels: Maybe Thermentioning

confidence: 99%

“… Proteins that were described in Lu, et al , [18], Sokolowski, et al ., [212], Kathiresan, et al , [213] and Kundu, et al ., [214] that reported proteins that directly associate with BK via proteomic methods were analyzed by REMBRANDT to determine whether that gene’s up-regulation or down-regulation could be predictive of glioma patient outcomes for either a good prognosis or a bad prognosis. Significance denotes whether a positive or negative correlation occurred (P <0.05).…”

Section: Figurementioning

confidence: 99%

Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy

Hoa

Wilson

et al. 2014

International Immunopharmacology

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The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, Stretch-activated potassium channels, KCa1.1). Each name reflects a different physical property displayed by this single ion channel. This transmembrane channel is found on nearly every cell type of the body and has its own distinctive roles for that tissue type. The BKα channel contains the pore that releases potassium ions from intracellular stores. This ion channel is found on the cell membrane, endoplasmic reticulum, Golgi and mitochondria. Complex splicing pathways produce different isoforms. The BKα channels can be phosphorylated, palmitoylated and myristylated. BK is composed of a homo-tetramer that interacts with β and γ chains. These accessory proteins provide a further modulating effect on the functions of BKα channels. BK channels play important roles in cell division and migration. In this review, we will focus on the biology of BK channels, especially its role, and that it has in the immune response towards cancer. Recent proteomic studies have linked BK channels with various proteins. Some of these interactions offer further insight into the role that BK channels have with cancers, especially with brain tumors. This review shows that BK channels have a complex interplay with intracellular components of cancer cells and still have plenty of secrets to be discovered.

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BK Channels: Regulation of Expression and Physiological Impact

Cited by 2 publications

References 121 publications

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain

Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy

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