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Last update 23 Jan 2025

Kir3.4

Last update 23 Jan 2025

Basic Info

Synonyms

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

+ [13]

Introduction

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.

Drugs associated with Kir3.4

IKACh blocking peptibody(University of South Florida)

Target

Kir3.1 x Kir3.4

Mechanism

Kir3.1 inhibitors [+1]

Active Org.

University of South Florida

Originator Org.

University of South Florida

Active Indication

Arrhythmias, Cardiac

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GIRK1/4 inhibitor (Novartis)

Target

Kir3.1 x Kir3.4

Mechanism

Kir3.1 inhibitors [+1]

Active Org.

Novartis Institutes for Biomedical Research, Inc.

Originator Org.

Novartis Institutes for Biomedical Research, Inc.

Active Indication

Atrial Fibrillation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AZD-2927

Target

Kir3.1 x Kir3.4

Mechanism

Kir3.1 inhibitors [+1]

Active Org.-

Originator Org.

AstraZeneca Pharmaceuticals Co. Ltd.

Active Indication-

Inactive Indication

Arrhythmias, Cardiac

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Kir3.4

NCT01396226

/ CompletedPhase 2

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

Start Date01 Sep 2011

Sponsor / Collaborator

AstraZeneca PLC

NCT01264250

/ CompletedPhase 1

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.

Start Date01 Jan 2011

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Kir3.4

100 Translational Medicine associated with Kir3.4

0 Patents (Medical) associated with Kir3.4

830

Literatures (Medical) associated with Kir3.4

01 Jan 2025·Hypertension

Evolutionary Characteristics in Primary Aldosteronism Patients

Article

Author: Chang, Xiaoyan ; Tong, Anli ; Nie, Min ; Wang, Yu ; Gao, Yinjie ; Zhou, Yue ; Zhang, Yushi

BACKGROUND:Primary aldosteronism is predominantly caused by excessive aldosterone production from the adrenal cortex, and the aldosterone-producing structures could take many forms, like adenomas, nodules, micronodules, and so on. Most studies of primary aldosteronism were limited to the hotspot driver genes responsible for autonomous aldosterone production; however, the panoramic genetic architecture and genomic alterations of aldosterone-producing structures and their adjacent hyperplasia glands remain unknown.METHODS:In this study, whole-exome sequencing and transcriptome sequencing (RNA-seq) analyses were performed using functional nodules and matched hyperplasia tissues, which were microdissected guided by aldosterone synthase immunohistochemistry. Phylogenetic trees were constructed based on the shared and unique mutations, gene mutation spectrums, and clonal characteristics.RESULTS: The rates of mutations represented higher means of functional nodules than hyperplasia samples, and the little mutational overlap was shown between the 2 groups on phylogenetic trees. The mutations of the aldosterone driver gene ( KCNJ5 or CACNA1D ) were only observed in functional nodules and indicated almost the largest values of cancer cell fraction. Moreover, the functional nodules also harbored some potential variants related to cell proliferation, which were not detected in hyperplasia tissues. Transcriptome analysis suggested that only 25.5% upregulated and 23.3% downregulated genes overlapped between functional nodules and hyperplasia tissues. CONCLUSIONS:This study demonstrated a genetic and transcriptome landscape of aldosterone-producing structures and adjacent hyperplasia glands in primary aldosteronism. The results indicated independent clonal origins on functional nodules and hyperplasia tissues, and little mutual evolutionary relationship was found on their phylogenetic trees.

01 Dec 2024·Hypertension

Somatic GNAQ , CTNNB1 , and CACNA1C Mutations in Cat Aldosterone-Secreting Tumors

Article

Author: Syme, Harriet ; Brown, Morris ; Watson, Alice

BACKGROUND: Primary aldosteronism (PA) is a common cause of human hypertension. Somatic mutations in KCNJ5 , CACNA1D , ATP1A1 , and ATP2B3 are found in at least 80% of aldosterone-producing adenomas, which cause unilateral PA in humans. Somatic mutations have been identified infrequently in 7 other genes; few of these were known to play a role in aldosterone secretion before the discovery of their mutations. Interrogating somatic mutations in the domestic cat, in which spontaneous PA is also known to occur, might improve the understanding of normal adrenal gland physiology and the pathophysiology of PA. METHODS:DNA and RNA extracted from tissue from 13 cats with unilateral aldosterone-secreting tumors, including 8 carcinomas and 5 adenomas, underwent whole genome sequencing, targeted Sanger sequencing, and RNA sequencing. Single-nucleotide substitution variants were filtered to select those with a predicted deleterious effect on protein function and a suspected role in aldosterone secretion.RESULTS: Probable functional somatic single-nucleotide polymorphisms (n=8) were found in 3 adenomas and 2 carcinomas. Mutations with predicted significant effects were identified in 2 genes also mutated in human PA; GNAQ and CTNNB1 , and in a residue of CACNA1C analogous to a common CACNA1D mutation. In contrast to humans, CACNA1C expression was much greater than CACNA1D in both feline tumor and nontumor adrenal tissue. No mutations were identified in KCNJ5 , CACNA1D , ATP1A1 , or ATP2B3.CONCLUSIONS:Similar mutations were identified in cats to those found in humans. It is, therefore, likely that both species have shared underlying selection pressures for mutations that increase aldosterone secretion.

07 Nov 2024·JCEM Case Reports

Aldosterone-producing Multiple Micronodules With Several Different KCNJ5 Pathogenic Variants

Article

Author: Aiga, Ko ; Kometani, Mitsuhiro ; Yoneda, Takashi ; Usukura, Mikiya ; Asano, Takahiro ; Oiwa, Yasushi

AbstractPrimary aldosteronism (PA) is the most common form of secondary hypertension. Recently, the genetic analysis of aldosterone-producing adenoma, a major cause of PA, has revealed several causative genes. Herein, we present a case of a 27-year-old Japanese female with PA. She was referred to our hospital with hypertension and hypokalemia (serum potassium, 2.8 mEq/L [2.8 mmol/L]). PA was diagnosed using several confirmatory tests. Computed tomography showed no apparent tumor in either adrenal gland. Adrenal vein sampling showed aldosterone overproduction in the right adrenal gland. Laparoscopic right adrenalectomy was performed, her blood pressure normalized, and the hypokalemia improved after surgery. Pathological findings revealed multiple aldosterone-producing micronodules with diameters of <5 mm. DNAs were extracted from 4 different micronodules and analyzed for KCNJ5. Two micronodules had a T158A pathogenic variant, 1 had a G151R pathogenic variant, and 1 had no pathogenic variant in the KCNJ5 gene. In summary, in our case, multiple nodules were present in 1 adrenal gland, and genetic heterogeneity was identified. No recurrence on the left side has been observed over 17 years following the surgery.

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Kir3.4

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