更新于：2024-11-01

BK channel x L-type calcium channel

更新于：2024-11-01

基本信息

关联

项与 BK channel x L-type calcium channel 相关的药物

Kakonein

葛根素

靶点

BK channel x L-type calcium channel

作用机制

BK channel激动剂 [+1]

在研机构

Natural Pharmacia International [+1]

原研机构

Natural Pharmacia International

在研适应症

心血管疾病 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期1993-01-01

Kakonein/Fructose

葛根素/果糖

靶点

BK channel x L-type calcium channel

作用机制

BK channel激动剂 [+1]

在研机构-

原研机构-

在研适应症

心绞痛 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

项与 BK channel x L-type calcium channel 相关的临床试验

ITMCTR2000003680 / SuspendedN/AIIT

Puerarin tablets in the treatment of endometriosis: a prospective, randomized, double-blind, multicenter clinical study

开始日期2020-10-01

申办/合作机构-

ChiCTR2000036735 / SuspendedN/AIIT

Puerarin tablets in the treatment of endometriosis: a prospective, randomized, double-blind, multicenter clinical study

开始日期2020-10-01

申办/合作机构-

ChiCTR1900022488 / Suspended早期临床1期IIT

A randomized controlled study for puerarin regulates gut microbiota of patients with carotid atherosclerosis

开始日期2019-05-01

申办/合作机构

南方医科大学珠江医院

100 项与 BK channel x L-type calcium channel 相关的临床结果

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100 项与 BK channel x L-type calcium channel 相关的转化医学

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0 项与 BK channel x L-type calcium channel 相关的专利（医药）

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项与 BK channel x L-type calcium channel 相关的文献（医药）

2023-08-22·Cells

Calcium-Activated Big-Conductance (BK) Potassium Channels Traffic through Nuclear Envelopes into Kinocilia in Ray Electrosensory Cells.

Article

作者: Shi, Lingfang ; Wu, Ting-Hsuan ; Kao, Peter N ; Clusin, William T ; Chen, Abby L

Electroreception through ampullae of Lorenzini in the little skate, Leucoraja erinacea, involves functional coupling between voltage-activated calcium channels (CaV1.3, cacna1d) and calcium-activated big-conductance potassium (BK) channels (BK, kcnma1). Whole-mount confocal microscopy was used to characterize the pleiotropic expression of BK and CaV1.3 in intact ampullae. BK and CaV1.3 are co-expressed in electrosensory cell plasma membranes, nuclear envelopes and kinocilia. Nuclear localization sequences (NLS) were predicted in BK and CaV1.3 by bioinformatic sequence analyses. The BK NLS is bipartite, occurs at an alternative splice site for the mammalian STREX exon and contains sequence targets for post-translational phosphorylation. Nuclear localization of skate BK channels was characterized in heterologously transfected HEK293 cells. Double-point mutations in the bipartite NLS (KR to AA or SVLS to AVLA) independently attenuated BK channel nuclear localization. These findings support the concept that BK partitioning between the electrosensory cell plasma membrane, nucleus and kinocilium may be regulated through a newly identified bipartite NLS.

2022-01-01·The Journal of Physiology2区 · 医学

Chronic stress facilitates bursting electrical activity in pituitary corticotrophs

2区 · 医学

Article

作者: Peter J Duncan ; Paul Le Tissier ; Mehran Fazli ; Nicola Romanò ; Richard Bertram ; Michael J Shipston

AbstractCoordination of an appropriate stress response is dependent upon anterior pituitary corticotroph excitability in response to hypothalamic secretagogues and glucocorticoid negative feedback. A key determinant of corticotroph excitability is large conductance calcium‐ and voltage‐activated (BK) potassium channels that are critical for promoting corticotrophin‐releasing hormone (CRH)‐induced bursting that enhances adrenocorticotrophic hormone secretion. Previous studies revealed hypothalamic–pituitary–adrenal axis hyperexcitability following chronic stress (CS) is partly a function of increased corticotroph output. Thus, we hypothesise that chronic stress promotes corticotroph excitability through a BK‐dependent mechanism. Corticotrophs from CS mice displayed significant increase in spontaneous bursting, which was suppressed by the BK blocker paxilline. Mathematical modelling reveals that the time constant of BK channel activation, plus properties and proportion of BK channels functionally coupled to L‐type Ca2+ channels determines bursting activity. Surprisingly, CS corticotrophs (but not unstressed) display CRH‐induced bursting even when the majority of BK channels are inhibited by paxilline, which modelling suggests is a consequence of the stochastic behaviour of a small number of BK channels coupled to L‐type Ca2+ channels. Our data reveal that changes in the stochastic behaviour of a small number of BK channels can finely tune corticotroph excitability through stress‐induced changes in BK channel properties. Importantly, regulation of BK channel function is highly context dependent allowing dynamic control of corticotroph excitability over a large range of time domains and physiological challenges in health and disease. This is likely to occur in other BK‐expressing endocrine cells, with important implications for the physiological processes they regulate and the potential for therapy.Key points

Chronic stress (CS) is predicted to modify the electrical excitability of anterior pituitary corticotrophs.

Electrophysiological recordings from isolated corticotrophs from CS male mice display spontaneous electrical bursting behaviour compared to the tonic spiking behaviour of unstressed corticotrophs.

The increased spontaneous bursting from CS corticotrophs is BK‐dependent and mathematical modelling reveals that the time constant of activation, properties and proportion of BK channels functionally coupled to L‐type calcium channels determines the promotion of bursting activity.

CS (but not unstressed) corticotrophs display corticotrophin‐releasing hormone‐induced bursting even when the majority of BK channels are pharmacologically inhibited, which can be explained by the stochastic behaviour of a small number of BK channels with distinct properties.

Corticotroph excitability can be finely tuned by the stochastic behaviour of a small number of BK channels dependent on their properties and functional co‐localisation with L‐type calcium channels to control corticotroph excitability over diverse time domains and physiological challenges.

2019-11-01·The FASEB Journal

Expression of the LRRC52 g subunit (g2) may provide Ca²⁺‐independent activation of BK currents in mouse inner hair cells

Article

作者: Lang, Isabelle ; Jung, Martin ; Engel, Jutta ; Niemeyer, Barbara A. ; Ruth, Peter

Mammalian inner hair cells (IHCs) transduce sound into depolarization and transmitter release. Big conductance and voltage‐ and Ca2+‐activated K+ (BK) channels are responsible for fast membrane repolarization and small time constants of mature IHCs. For unknown reasons, they activate at around ‐75 mV with a voltage of half‐maximum activation (Vhalf) of ‐50 mV although being largely insensitive to Ca2+ influx. Ca2+‐independent activation of BK channels was observed by others in heterologous expression systems if γ subunits leucine‐rich repeat‐containing protein (LRRC)26 (γ1) and LRRC52 (γ2) were coexpressed with the pore‐forming BKα subunit, which shifted Vhalf by ‐140 and ‐100 mV, respectively. Using nested PCR, we consistently detected transcripts for LRRC52 but not for LRRC26 in IHCs of 3‐wk‐old mice. Confocal immunohistochemistry showed synchronous up‐regulation of LRRC52 protein with BKα at the onset of hearing. Colocalization of LRRC52 protein and BKα at the IHC neck within ≤40 nm was specified using an in situ proximity ligation assay. Mice deficient for the voltage‐gated Cav1.3 Ca2+ channel encoded by Cacna1d do not express BKα protein. LRRC52 protein was neither expressed in IHCs of BKα nor in IHCs of Cav1.3 knockout mice. Together, LRRC52 is a γ2 subunit of BK channel complexes and is a strong candidate for causing the Ca2+‐independent activation of BK currents at negative membrane potentials in mouse IHCs.—Lang, I., Jung, M., Niemeyer, B. A., Ruth, P., Engel, J. Expression of the LRRC52 γ subunit (γ2) may provide Ca2+‐independent activation of BK currents in mouse inner hair cells. FASEB J. 33, 11721‐11734 (2019). www.fasebj.org