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Last update 08 May 2025

KCNU1

Last update 08 May 2025

Basic Info

Synonyms

Calcium-activated potassium channel subunit alpha-3, Calcium-activated potassium channel, subfamily M subunit alpha-3, KCa5

+ [9]

Introduction

Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+) (PubMed:23129643, PubMed:24670955, PubMed:36649421, PubMed:38267364, PubMed:9452476). Represents the primary spermatozoan K(+) current. The channel underlies a pH-triggered membrane hyperpolarization during the process of sperm capacitation, as sperm encounter the alkaline environment near the ovum in the female reproductive tract, thereby playing an essential for male fertility (PubMed:34980136, PubMed:35551387, PubMed:36649421).

Drugs associated with KCNU1

VU0546110

Target

KCNU1

Mechanism

KCNU1 blockers

Active Org.

Washington University in St. Louis

Originator Org.

Washington University in St. Louis

Active Indication

Contraception

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KCNU1

100 Translational Medicine associated with KCNU1

0 Patents (Medical) associated with KCNU1

Literatures (Medical) associated with KCNU1

01 Feb 2025·Poultry Science

The hematopoietic function, histological characteristics, and transcriptome profiling of Wanxi white geese ovary during nesting and late-laying stages

Article

Author: She, Deyong ; Zhao, Chunfang ; Jin, Tao ; Liu, Xinyu ; Yang, Kefeng ; Li, Shenghe ; Hu, Qianqian ; Ren, Man

Despite several factors influencing reproduction in geese, but the precise molecular mechanisms of egg cessation are not fully understood. In the present study, the hematopoietic parameters and serum hormone levels in Wanxi white geese were analyzed. RNA-Seq was utilized to identify the differentially expressed mRNAs (DEGs) and lncRNAs (DE lncRNAs) in the ovarian tissues associated with nesting in geese during the late-laying and nesting periods. Triglyceride (TG) and alkaline phosphatase (ALP) levels were higher in late-laying geese, while white blood cell (WBC), neutrophil (NEU), hemoglobin (HGB), and hematocrit (HCT) levels were significantly lower in late-laying geese. Serum levels of luteinizing hormone (LH), estrogen (E2), and progesterone (P4) increased significantly during the late-laying period, whereas prolactin (PRL) level was lower in the late-laying period than the nesting period. During the late-laying period, geese had a clear follicular hierarchy, with ovaries exhibiting mature and primary follicles. In the nesting period, the ovaries were degenerated and had many primary follicles without follicular development. Analysis of mRNA-lncRNA expression revealed 1,257 DEGs between the nesting and the late-laying stages, of which 841 were up-regulated and 416 were down-regulated DEGs. A total of 340 DE lncRNAs were identified between the nesting and the late-laying periods, with 113 being up-regulated and 227 down-regulated lncRNAs. DEGs, including TMEM, DRD3, IGFBP7, MAPK13, GnRHR2, HECTD3, KCNU1, OPRD1, and VCAM1, along with DE lncRNAs, including XR_001203613.1, XR_001206155.1, XR_001207759.1, XR_001213571.1 and XR_001214368.1 participate in reproduction in geese. Correlation analysis indicated that the cis-regulation of XR_001213096.1-ITPR3, XR_001203613.1-GALNT15, XR_001206155.1-COL6A3, XR_001207759.1-ANKS1B, and XR_001214368.1-VPS45 participate in the molecular mechanisms underlying nesting in geese. Functional enrichment analysis revealed the DEGs and DE lncRNAs associated with focal adhesion, extracellular matrix (ECM)-receptor interaction, cell adhesion molecules (CAMs), and PI3K-Akt signaling pathways, were responsible for the differences in the ovaries between the nesting and late-laying periods. This study offers valuable information on the roles of genes and lncRNAs, and the mechanisms underlying variations in reproductive performance between the late-laying and nesting periods.

01 Feb 2025·Andrology

Physiological role of potassium channels in mammalian germ cell differentiation, maturation, and capacitation

Review

Author: Yeste, Marc ; Delgado‐Bermúdez, Ariadna ; Bonet, Sergi ; Pinart, Elisabeth

AbstractBackgroundIon channels are essential for differentiation and maturation of germ cells, and even for fertilization in mammals. Different types of potassium channels have been identified, which are grouped into voltage‐gated channels (Kv), ligand‐gated channels (Kligand), inwardly rectifying channels (Kir), and tandem pore domain channels (K2P).Material‐MethodsThe present review includes recent findings on the role of potassium channels in sperm physiology of mammals.Results‐DiscussionWhile most studies conducted thus far have been focused on the physiological role of voltage‐ (Kv1, Kv3, and Kv7) and calcium‐gated channels (SLO1 and SLO3) during sperm capacitation, especially in humans and rodents, little data about the types of potassium channels present in the plasma membrane of differentiating germ cells exist. In spite of this, recent evidence suggests that the content and regulation mechanisms of these channels vary throughout spermatogenesis. Potassium channels are also essential for the regulation of sperm cell volume during epididymal maturation and for preventing premature membrane hyperpolarization. It is important to highlight that the nature, biochemical properties, localization, and regulation mechanisms of potassium channels are species‐specific. In effect, while SLO3 is the main potassium channel involved in the K+ current during sperm capacitation in rodents, different potassium channels are implicated in the K+ outflow and, thus, plasma membrane hyperpolarization during sperm capacitation in other mammalian species, such as humans and pigs.ConclusionsPotassium conductance is essential for male fertility, not only during sperm capacitation but throughout the spermiogenesis and epididymal maturation.

01 Dec 2024·Journal of Biological Chemistry

The sodium–proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm

Article

Author: Treviño, Claudia L. ; Luque, Guillermina M ; Buffone, Mariano G ; Krapf, Dario ; Treviño, Claudia L ; De la Vega Beltrán, José L ; Carruba, Micaela ; De la Vega Beltrán, José L. ; Buffone, Mariano G. ; Gentile, Iñaki ; Novero, Analia G ; Krapf, Diego ; Ritagliati, Carla ; Schiavi-Ehrenhaus, Liza J. ; Torres Rodríguez, Paulina ; Luque, Guillermina M. ; Nishigaki, Takuya ; Schiavi-Ehrenhaus, Liza J ; Rodríguez, Paulina Torres ; Stival, Cintia ; Novero, Analia G. ; Santi, Celia M ; Darszon, Alberto ; Santi, Celia M.

Sperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components, such as bicarbonate, albumin, Ca²⁺, and energy substrates, among others. Genetic and pharmacological studies have underscored the unique significance of the K⁺ channel SLO3 in membrane potential hyperpolarization, as evidenced by the infertility of mice lacking its expression. Notably, two key molecular events, sperm hyperpolarization and intracellular alkalinization, are central to the capacitation process. SLO3 is activated by alkalinization. However, the molecular mechanisms responsible for intracellular alkalization and activation of SLO3 are not completely understood. In this study, we examined the impact of Na⁺/H⁺ exchangers (NHEs) on mouse sperm membrane hyperpolarization during capacitation. Pharmacological inhibition of the NHE1 blocked membrane hyperpolarization. A similar effect was observed in sperm deficient of the Ca²⁺ channel CatSper because of NHE1 not being activated by Ca²⁺. In addition, the sperm-specific NHE (sNHE) KO did not show membrane hyperpolarization upon capacitation or induction with cAMP analogs. Our results show that sNHE is dually modulated by cAMP and membrane hyperpolarization probably through its cyclic nucleotide-binding domain and the voltage-sensor motif, respectively. Together, sNHE and NHE1 provide the alkalinization need for SLO3 activation during capacitation.

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KCNU1

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