ijms-logo

Journal Browser

Journal Browser

Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 January 2021) | Viewed by 30150

Special Issue Editor


E-Mail Website
Guest Editor
Unit of Cell Biology, Biotechnology of Animal and Human Reproduction (TechnoSperm), Department of Biology, Faculty of Sciences, Institute of Food and Agricultural Technology, University of Girona, E-17003 Girona, Spain
Interests: sperm physiology; flow cytometry; sperm motility; boar reproduction; sperm maturation; sperm capacitation; ion channels; immunocytochemistry; sperm cryopreservation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels exert a fundamental role in sperm physiology and fertilization; therefore, they modulate homeostasis, motility, chemotaxis towards the egg, and acrosome reaction. Moreover, during their journey to the egg, sperm cells go through different media with a distinct ionic composition, which require continuous cell adaptation and changes in the activity of ion channels.

Different types of ion channels with distinct activation and regulation mechanisms are present in the plasma membrane of mammal and nonmammal spermatozoa, which express sequentially throughout spermatogenesis. Recent studies on marine and mammal spermatozoa have focused on the functional role of calcium, potassium, and proton channels during sperm capacitation and their relationship with plasma membrane hyperpolarization, hyperactivation of sperm motility, and acrosome reaction. Interestingly, some types of ion channels are present in most species but differing in their content and regulation mechanisms, thus highlighting that sperm physiology is species-specific.

This issue of IJMS is focused on “Ion Channels of Spermatozoa: Structure, Function, and Regulation Mechanisms” and therefore welcomes novel research or insightful reviews on the role of ion channels in sperm function. Submissions dealing with the effects of pathologies or sperm processing in ion channel function, as well as comparisons in ion channel content and function between species are also welcomed.

Prof. Elisabeth Pinart
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Sperm physiology
  • Spermatogenesis
  • Sperm maturation
  • Sperm capacitation
  • Plasma membrane potential
  • Ionic conductance
  • Cryopreservation
  • Sperm sample processing
  • Fertilization

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 548 KiB  
Editorial
Ion Channels of Spermatozoa: Structure, Function, and Regulation Mechanisms
by Elisabeth Pinart
Int. J. Mol. Sci. 2022, 23(11), 5880; https://doi.org/10.3390/ijms23115880 - 24 May 2022
Cited by 1 | Viewed by 1656
Abstract
Ion transport is essential for sperm physiology, being involved in sperm-cell differentiation and maturation, motility activation, chemotaxis towards the oocyte, and fertilization, as well as in sperm adaptation to the surrounding medium [...] Full article
Show Figures

Figure 1

Research

Jump to: Editorial, Review

12 pages, 2859 KiB  
Article
Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa
by Giulia Poli, Sonia Hasan, Silvia Belia, Marta Cenciarini, Stephen J. Tucker, Paola Imbrici, Safa Shehab, Mauro Pessia, Stefano Brancorsini and Maria Cristina D'Adamo
Int. J. Mol. Sci. 2021, 22(11), 5972; https://doi.org/10.3390/ijms22115972 - 1 Jun 2021
Cited by 6 | Viewed by 3497
Abstract
The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K+ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H+ (pHi) and extracellular K+ concentration [K+]o [...] Read more.
The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K+ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H+ (pHi) and extracellular K+ concentration [K+]o, and hence provides a link between pHi and [K+]o changes and membrane potential. The intrinsic pHi sensitivity of Kir5.1 suggests a possible role for this channel in the pHi-dependent processes that take place during fertilization. However, despite the localization of Kir5.1 in murine spermatozoa, and its increased expression with age and sexual maturity, the role of the channel in sperm morphology, maturity, motility, and fertility is unknown. Here, we confirmed the presence of Kir5.1 in spermatozoa and showed strong expression of Kir4.1 channels in smooth muscle and epithelial cells lining the epididymal ducts. In contrast, Kir4.2 expression was not detected in testes. To examine the possible role of Kir5.1 in sperm physiology, we bred mice with a deletion of the Kcnj16 (Kir5.1) gene and observed that 20% of Kir5.1 knock-out male mice were infertile. Furthermore, 50% of knock-out mice older than 3 months were unable to breed. By contrast, 100% of wild-type (WT) mice were fertile. The genetic inactivation of Kcnj16 also resulted in smaller testes and a greater percentage of sperm with folded flagellum compared to WT littermates. Nevertheless, the abnormal sperm from mutant animals displayed increased progressive motility. Thus, ablation of the Kcnj16 gene identifies Kir5.1 channel as an important element contributing to testis development, sperm flagellar morphology, motility, and fertility. These findings are potentially relevant to the understanding of the complex pHi- and [K+]o-dependent interplay between different sperm ion channels, and provide insight into their role in fertilization and infertility. Full article
Show Figures

Figure 1

17 pages, 1872 KiB  
Article
Inhibition of Potassium Channels Affects the Ability of Pig Spermatozoa to Elicit Capacitation and Trigger the Acrosome Exocytosis Induced by Progesterone
by Federico Noto, Sandra Recuero, Julián Valencia, Beatrice Saporito, Domenico Robbe, Sergi Bonet, Augusto Carluccio and Marc Yeste
Int. J. Mol. Sci. 2021, 22(4), 1992; https://doi.org/10.3390/ijms22041992 - 17 Feb 2021
Cited by 8 | Viewed by 3157
Abstract
During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial [...] Read more.
During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial for capacitation of mouse and human sperm, their role in pigs has not been investigated. With this purpose, sperm samples from 15 boars were incubated in capacitation medium for 300 min with quinine, a general blocker of potassium channels (including voltage-gated potassium channels, calcium-activated potassium channels, and tandem pore domain potassium channels), and paxilline (PAX), a specific inhibitor of calcium-activated potassium channels. In all samples, acrosome exocytosis was induced after 240 min of incubation with progesterone. Plasma membrane and acrosome integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and total and progressive sperm motility were evaluated after 0, 120, and 240 min of incubation, and after 5, 30, and 60 min of progesterone addition. Although blocking potassium channels with quinine and PAX prevented sperm to elicit in vitro capacitation by impairing motility and mitochondrial function, as well as reducing intracellular calcium levels, the extent of that inhibition was larger with quinine than with PAX. Therefore, while our data support that calcium-activated potassium channels are essential for sperm capacitation in pigs, they also suggest that other potassium channels, such as the voltage-gated, tandem pore domain, and mitochondrial ATP-regulated ones, are involved in that process. Thus, further research is needed to elucidate the specific functions of these channels and the mechanisms underlying its regulation during sperm capacitation. Full article
Show Figures

Figure 1

17 pages, 4761 KiB  
Article
HVCN1 but Not Potassium Channels Are Related to Mammalian Sperm Cryotolerance
by Ariadna Delgado-Bermúdez, Yentel Mateo-Otero, Marc Llavanera, Sergi Bonet, Marc Yeste and Elisabeth Pinart
Int. J. Mol. Sci. 2021, 22(4), 1646; https://doi.org/10.3390/ijms22041646 - 6 Feb 2021
Cited by 3 | Viewed by 2175
Abstract
Little data exist about the physiological role of ion channels during the freeze–thaw process in mammalian sperm. Herein, we determined the relevance of potassium channels, including SLO1, and of voltage-gated proton channels (HVCN1) during mammalian sperm cryopreservation, using the pig as a model [...] Read more.
Little data exist about the physiological role of ion channels during the freeze–thaw process in mammalian sperm. Herein, we determined the relevance of potassium channels, including SLO1, and of voltage-gated proton channels (HVCN1) during mammalian sperm cryopreservation, using the pig as a model and through the addition of specific blockers (TEA: tetraethyl ammonium chloride, PAX: paxilline or 2-GBI: 2-guanidino benzimidazole) to the cryoprotective media at either 15 °C or 5 °C. Sperm quality of the control and blocked samples was performed at 30- and 240-min post-thaw, by assessing sperm motility and kinematics, plasma and acrosome membrane integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and intracellular O2⁻ and H2O2 levels. General blockade of K+ channels by TEA and specific blockade of SLO1 channels by PAX did not result in alterations in sperm quality after thawing as compared to control samples. In contrast, HVCN1-blocking with 2-GBI led to a significant decrease in post-thaw sperm quality as compared to the control, despite intracellular O2⁻ and H2O2 levels in 2-GBI blocked samples being lower than in the control and in TEA- and PAX-blocked samples. We can thus conclude that HVCN1 channels are related to mammalian sperm cryotolerance and have an essential role during cryopreservation. In contrast, potassium channels do not seem to play such an instrumental role. Full article
Show Figures

Figure 1

12 pages, 6360 KiB  
Article
Na+/H+ Exchangers Involve in Regulating the pH-Sensitive Ion Channels in Mouse Sperm
by Hang Kang, Min Liu, Wei Zhang, Rong-Zu Huang, Na Zhao, Chen Chen and Xu-Hui Zeng
Int. J. Mol. Sci. 2021, 22(4), 1612; https://doi.org/10.3390/ijms22041612 - 5 Feb 2021
Cited by 14 | Viewed by 2206
Abstract
Sperm-specific K+ ion channel (KSper) and Ca2+ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca2+ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through [...] Read more.
Sperm-specific K+ ion channel (KSper) and Ca2+ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca2+ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through the alkaline environment of the female reproductive tract. However, which intracellular pH (pHi) regulator functionally couples to the activation of KSper/CatSper remains obscure. Although Na+/H+ exchangers (NHEs) have been implicated to mediate pHi in sperm, there is a lack of direct evidence confirming the functional coupling between NHEs and KSper/CatSper. Here, 5-(N,N-dimethyl)-amiloride (DMA), an NHEs inhibitor that firstly proved not to affect KSper/CatSper directly, was chosen to examine NHEs function on KSper/CatSper in mouse sperm. The results of patch clamping recordings showed that, when extracellular pH was at the physiological level of 7.4, DMA application caused KSper inhibition and the depolarization of membrane potential when pipette solutions were not pH-buffered. In contrast, these effects were minimized when pipette solutions were pH-buffered, indicating that they solely resulted from pHi acidification caused by NHEs inhibition. Similarly, DMA treatment reduced CatSper current and intracellular Ca2+, effects also dependent on the buffer capacity of pH in pipette solutions. The impairment of sperm motility was also observed after DMA incubation. These results manifested that NHEs activity is coupled to the activation of KSper/CatSper under physiological conditions. Full article
Show Figures

Figure 1

15 pages, 2610 KiB  
Article
Polyamines Influence Mouse Sperm Channels Activity
by Lorena Rodríguez-Páez, Charmina Aguirre-Alvarado, Norma Oviedo, Verónica Alcántara-Farfán, Edgar E. Lara-Ramírez, Guadalupe Elizabeth Jimenez-Gutierrez and Joaquín Cordero-Martínez
Int. J. Mol. Sci. 2021, 22(1), 441; https://doi.org/10.3390/ijms22010441 - 4 Jan 2021
Cited by 6 | Viewed by 3629
Abstract
Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events [...] Read more.
Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events that improve sperm motility and capacitation. In the present work, we hypothesize about the influence of polyamines, namely, spermine, spermidine, and putrescine, on the activity of sperm channels, evaluating the intracellular concentrations of chloride [Cl]i, calcium [Ca2+]i, sodium [Na+]i, potassium [K+]i, the membrane Vm, and pHi. The aim of this is to identify the possible regulatory mechanisms mediated by the polyamines on sperm-specific channels under capacitation and non-capacitation conditions. The results showed that the presence of polyamines did not directly influence the activity of calcium and chloride channels. However, the results suggested an interaction of polyamines with sodium and potassium channels, which may contribute to the membrane Vm during capacitation. In addition, alkalization of the pHi revealed the possible activation of sperm-specific Na+/H+ exchangers (NHEs) by the increased levels of cyclic AMP (cAMP), which were produced by soluble adenylate cyclase (sAC) and interact with the polyamines, evidence that is supported by in silico analysis. Full article
Show Figures

Graphical abstract

22 pages, 5420 KiB  
Article
HVCN1 Channels Are Relevant for the Maintenance of Sperm Motility During In Vitro Capacitation of Pig Spermatozoa
by Marc Yeste, Marc Llavanera, Yentel Mateo-Otero, Jaime Catalán, Sergi Bonet and Elisabeth Pinart
Int. J. Mol. Sci. 2020, 21(9), 3255; https://doi.org/10.3390/ijms21093255 - 4 May 2020
Cited by 23 | Viewed by 3453
Abstract
The objective of the present study was to determine the physiological role of voltage-gated hydrogen channels 1 (HVCN1 channels) during in vitro capacitation of pig spermatozoa. Sperm samples from 20 boars were incubated in capacitating medium for 300 minutes (min) in the presence [...] Read more.
The objective of the present study was to determine the physiological role of voltage-gated hydrogen channels 1 (HVCN1 channels) during in vitro capacitation of pig spermatozoa. Sperm samples from 20 boars were incubated in capacitating medium for 300 minutes (min) in the presence of 2-guanidino benzimidazole (2-GBI), a specific HVCN1-channel blocker, added either at 0 min or after 240 min of incubation. Control samples were incubated in capacitating medium without the inhibitor. In all samples, acrosomal exocytosis was triggered with progesterone after 240 min of incubation. Sperm viability, sperm motility and kinematics, acrosomal exocytosis, membrane lipid disorder, intracellular calcium levels and mitochondrial membrane potential were evaluated after 0, 60, 120, 180, 240, 250, 270 and 300 min of incubation. While HVCN1-blockage resulted in altered sperm viability, sperm motility and kinematics and reduced mitochondrial membrane potential as compared to control samples, at any blocker concentration and incubation time, it had a non-significant effect on intracellular Ca2+ levels determined through Fluo3-staining. The effects on acrosomal exocytosis were only significant in blocked samples at 0 min, and were associated with increased membrane lipid disorder and Ca2+ levels of the sperm head determined through Rhod5-staining. In conclusion, HVCN1 channels play a crucial role in the modulation of sperm motility and kinematics, and in Ca2+ entrance to the sperm head. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 2363 KiB  
Review
Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review
by Marina Ramal-Sanchez, Nicola Bernabò, Luca Valbonetti, Costanza Cimini, Angela Taraschi, Giulia Capacchietti, Juliana Machado-Simoes and Barbara Barboni
Int. J. Mol. Sci. 2021, 22(9), 4306; https://doi.org/10.3390/ijms22094306 - 21 Apr 2021
Cited by 19 | Viewed by 3791
Abstract
Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The [...] Read more.
Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, were described to date in different species and cell types. Moreover, all those modulators with a relationship with the reproductive process, either found in the female tract, seminal plasma, or spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is one of the most intriguing and less understood events of the fertilization process, in the present work, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some pathologies in mammals strictly related to the male reproductive system. Full article
Show Figures

Figure 1

16 pages, 879 KiB  
Review
Role of the Glycosylphosphatidylinositol-Anchored Protein TEX101 and Its Related Molecules in Spermatogenesis
by Hiroshi Yoshitake and Yoshihiko Araki
Int. J. Mol. Sci. 2020, 21(18), 6628; https://doi.org/10.3390/ijms21186628 - 10 Sep 2020
Cited by 10 | Viewed by 5392
Abstract
Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) on the plasma membrane are involved in several cellular processes, including sperm functions. Thus far, several GPI-APs have been identified in the testicular germ cells, and there is increasing evidence of their biological significance during fertilization. Among GPI-APs identified [...] Read more.
Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) on the plasma membrane are involved in several cellular processes, including sperm functions. Thus far, several GPI-APs have been identified in the testicular germ cells, and there is increasing evidence of their biological significance during fertilization. Among GPI-APs identified in the testis, this review focuses on TEX101, a germ cell-specific GPI-AP that belongs to the lymphocyte antigen 6/urokinase-type plasminogen activator receptor superfamily. This molecule was originally identified as a glycoprotein that contained the antigen epitope for a specific monoclonal antibody; it was produced by immunizing female mice with an allogenic testicular homogenate. This review mainly describes the current understanding of the biochemical, morphological, and physiological characteristics of TEX101. Furthermore, future avenues for the investigation of testicular GPI-Aps, including their potential role as regulators of ion channels, are discussed. Full article
Show Figures

Figure 1

Back to TopTop