+mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in the adult mouse brain

Zhang, Yingying; Han, Xue; Liu, Ye; Chen, Jian; Lu, Hua; Ma, Qian; Huang, Yangyuxin; Tang, Qiong-Yao; Zhang, Zhe

doi:10.1371/journal.pone.0191749

“…Although mRNA expression suggests that γ2 expression is limited to testis and sperm in both mice and humans, the ability of LRRC52 to shift BK gating approximately −100 mV at 0 Ca 2+ leaves open the possibility that it may partner with Slo1 subunits in some unidentified loci. For γ3 (LRRC55), message distribution (97, 112) and in situ hybridization (113) suggest potential roles in excitable cells, although γ3-induced gating shifts are modest compared to those in both γ1 and γ2 (97). At present, γ3 remains simply an interesting candidate for a BK regulatory subunit.…”

Section: A Bit Of History: the Bk Channel α Subunitmentioning

confidence: 99%

Regulation of BK Channels by Beta and Gamma Subunits

González-Pérez

¹

,

Lingle

²

2019

Annu. Rev. Physiol.

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Ca2+- and voltage-gated K+ channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore–forming α subunit (KCa1.1, Kcnma1, Slo1) gene, two families of regulatory subunits, β and γ, define BK channels that span a diverse range of functional properties. We are just beginning to unravel the cell-specific, physiological roles served by BK channels of different subunit composition.

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“…These can modify activity, including modifying sensitivity to its activators, voltage or Ca 2+ , or by activating protein kinases 111 . Furthermore, the association with γ subunits, which are leucine rich repeat containing proteins, can increase stimulability of the BK channel by decreasing the negative voltage difference threshold 112 . Ultimately, this increases the range of pharmacological applications of these channels.…”

Section: Bk Channels Reduce Excitotoxic Stressmentioning

confidence: 99%

Oligodendrocytes, BK channels and the preservation of myelin

Rupnik

¹

,

Baker

²

,

Selwood

³

2021

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Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2+-activated K+ channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies.

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“…These can modify activity, including modifying sensitivity to its activators, voltage or Ca 2+ , or by activating protein kinases 99 . Furthermore, the association with γ subunits, which are leucine rich repeat containing proteins, can increase stimulability of the BK channel by decreasing the negative voltage difference threshold 100 . Ultimately, this increases the range of pharmacological applications of these channels.…”

Section: Bk Channels Reduce Excitotoxic Stress Bk Channelsmentioning

confidence: 99%

Oligodendrocytes, BK channels and remyelination

Rupnik

¹

,

Baker

²

,

Selwood

³

2021

F1000Res

1

0

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Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2+-activated K+ channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies.

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+mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in the adult mouse brain

Cited by 9 publications

References 31 publications

Regulation of BK Channels by Beta and Gamma Subunits

Regulation of BK Channels by Beta and Gamma Subunits

Oligodendrocytes, BK channels and the preservation of myelin

Oligodendrocytes, BK channels and remyelination

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