更新于：2024-11-01

Kir3.4

更新于：2024-11-01

基本信息

别名

Cardiac inward rectifier、CIR、G protein-activated inward rectifier potassium channel 4

+ [13]

简介

This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium.

关联

项与 Kir3.4 相关的药物

GIRK1/4 inhibitor (Novartis)

靶点

Kir3.1 x Kir3.4

作用机制

Kir3.1抑制剂 [+1]

在研机构

Novartis AG

原研机构

Novartis AG

在研适应症

心房颤动

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

IKACh blocking peptibody(University of South Florida)

靶点

Kir3.1 x Kir3.4

作用机制

Kir3.1抑制剂 [+1]

在研机构

University of South Florida

原研机构

University of South Florida

在研适应症

心律失常

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

AZD-2927

靶点

Kir3.1 x Kir3.4

作用机制

Kir3.1抑制剂 [+1]

在研机构-

原研机构

阿斯利康制药有限公司

在研适应症-

非在研适应症

心律失常

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 Kir3.4 相关的临床试验

NCT01396226 / Completed临床2期

A Multi-Centre, Double-Blind, Randomised, Placebo-Controlled Phase II Study to Assess the Effects on Atrial and Ventricular Refractoriness of an Intravenous Infusion of AZD2927 in Patients Undergoing an Invasive Electrophysiological Procedure

Medical Products Agency

开始日期2011-09-01

申办/合作机构

AstraZeneca PLC

NCT01264250 / Completed临床1期

A Phase I, Single-centre, Single-blind, Randomised, Placebo-controlled, Single-dose Study to Assess the Safety, Tolerability and Pharmacokinetics After Single Ascending Intravenous Doses of AZD2927 in Healthy Male Subjects

In this early phase study, healthy male volunteers will be randomly assigned to one dose of either AZD2927 or placebo. The objective will be to assess the Safety,Tolerability and Pharmacokinetics of AZD2927.

开始日期2011-01-01

申办/合作机构

AstraZeneca PLC

100 项与 Kir3.4 相关的临床结果

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100 项与 Kir3.4 相关的转化医学

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0 项与 Kir3.4 相关的专利（医药）

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805

项与 Kir3.4 相关的文献（医药）

2024-08-25·Sheng li xue bao : [Acta physiologica Sinica]

[Research progress of KCNJ5 gene in aldosterone-producing adenoma].

Review

作者: Hou, Ming-Shuang ; Yi, Lin ; Xu, Jing ; Li, Yong-Xiang ; Kou, Yu-Shun ; Teng, Zheng-Jie ; Li, Meng-Yao ; Chen, Qian-Qian ; Ma, Rui-Ling ; Lyu, Hong-Ying ; Jia, Guan-Jun

Aldosterone-producing adenoma is a subtype of primary aldosteronism. Recent advancements in multi-omics research have led to significant progress in understanding primary aldosteronism at the genetic level. Among the various genes associated with the development of aldosterone-producing adenomas, the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene has received considerable attention due to its prevalence as the most common somatic mutation gene in primary aldosteronism. This paper aims to integrate the existing evidence on the involvement of KCNJ5 gene in the pathogenesis of aldosterone-producing adenomas, to enhance the understanding of the underlying mechanisms of aldosterone-producing adenomas from the perspective of genetics, and to provide novel insights for the clinical diagnosis and treatment of aldosterone-producing adenomas.

2024-08-10·Internal medicine (Tokyo, Japan)

Primary aldosteronism and hypokalemia-induced rhabdomyolysis in a patient with aldosterone-producing adenoma: A case report and literature review.

Article

作者: Tani, Takashi ; Hasegawa, Go ; Yoneoka, Yuichiro ; Nakamura, Yasuhiro ; Terajima, Kenshi ; Nishiyama, Tsutomu ; Ozawa, Tetsutaro ; Shimada, Hiroki ; Ohara, Nobumasa

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

2024-07-01·Pflügers Archiv - European Journal of Physiology

Angiotensin receptors and α1B-adrenergic receptors regulate native IK(ACh) and phosphorylation-deficient GIRK4 (S418A) channels through different PKC isoforms

Article

作者: Kienitz, Marie-Cécile ; Inderwiedenstraße, Leonie

Signaling of G protein-activated inwardly rectifying K⁺ (GIRK) channels is an important mechanism of the parasympathetic regulation of the heart rate and cardiac excitability. GIRK channels are inhibited during stimulation of G_q-coupled receptors (G_qPCRs) by depletion of phosphatidyl-4,5-bisphosphate (PIP₂) and/or channel phosphorylation by protein kinase C (PKC). The G_qPCR-dependent modulation of GIRK currents in terms of specific PKC isoform activation was analyzed in voltage-clamp experiments in rat atrial myocytes and in CHO or HEK 293 cells. By using specific PKC inhibitors, we identified the receptor-activated PKC isoforms that contribute to phenylephrine- and angiotensin-induced GIRK channel inhibition. We demonstrate that the cPKC isoform PKCα significantly contributes to GIRK inhibition during stimulation of wildtype α_1B-adrenergic receptors (α_1B-ARs). Deletion of the α_1B-AR serine residues S³⁹⁶ and S⁴⁰⁰ results in a preferential regulation of GIRK activity by PKCβ. As a novel finding, we report that the AT₁-receptor-induced GIRK inhibition depends on the activation of the nPKC isoform PKCε whereas PKCα and PKCβ do not mainly participate in the angiotensin-mediated GIRK reduction. Expression of the dominant negative (DN) PKCε prolonged the onset of GIRK inhibition and significantly reduced AT₁-R desensitization, indicating that PKCε regulates both GIRK channel activity and the strength of the receptor signal via a negative feedback mechanism. The serine residue S⁴¹⁸ represents an important phosphorylation site for PKCε in the GIRK4 subunit. To analyze the functional impact of this PKC phosphorylation site for receptor-specific GIRK channel modulation, we monitored the activity of a phosphorylation-deficient (GIRK4 (S418A)) GIRK4 channel mutant during stimulation of α_1B-ARs or AT₁-receptors. Mutation of S⁴¹⁸ did not impede α_1B-AR-mediated GIRK inhibition, suggesting that S⁴¹⁸ within the GIRK4 subunit is not subject to PKCα-induced phosphorylation. Furthermore, activation of angiotensin receptors induced pronounced GIRK4 (S418A) channel inhibition, excluding that this phosphorylation site contributes to the AT₁-R-induced GIRK reduction. Instead, phosphorylation of S⁴¹⁸ has a facilitative effect on GIRK activity that was abolished in the GIRK4 (S418A) mutant. To summarize, the present study shows that the receptor-dependent regulation of atrial GIRK channels is attributed to the G_qPCR-specific activation of different PKC isoforms. Receptor-specific activated PKC isoforms target distinct phosphorylation sites within the GIRK4 subunit, resulting in differential regulation of GIRK channel activity with either facilitative or inhibitory effects on GIRK currents.