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Ion Channels in Sperm Physiology 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 31262

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Prof. Dr. Elisabeth Pinart

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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
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Dear Colleagues,

Ion channels exert a fundamental role in sperm physiology and fertilization; therefore, they modulate homeostasis, motility, chemotaxis toward 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 Special Issue of IJMS is the continuation of a previous Special Issue on “Ion Channels of Spermatozoa: Structure, Function, and Regulation Mechanisms”. Therefore, it welcomes novel research or insightful reviews on the role of ion channels in sperm function and physiology. 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.

I look forward to receiving your contributions.

Prof. Elisabeth Pinart
Guest Editor

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Keywords

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

Published Papers (12 papers)

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25 pages, 6956 KiB

Open AccessArticle

Role of Ion Channels in the Maintenance of Sperm Motility and Swimming Behavior in a Marine Teleost

by Júlia Castro-Arnau, François Chauvigné and Joan Cerdà

Int. J. Mol. Sci. 2022, 23(20), 12113; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012113 - 11 Oct 2022

Cited by 8 | Viewed by 1668

Abstract

In oviparous marine fishes, the hyperosmotic induction of sperm motility in seawater (SW) is well established, however, the potential function of ion channels in the maintenance of post activated spermatozoon swimming performance remains largely unknown. Here, we investigated the influence of ion channels on the spermatozoon swimming parameters using the gilthead seabream (Sparus aurata) as a model for modern marine teleosts. Our data show that the SW-induced activation of seabream sperm motility requires three concomitant processes, the hyperosmotic shock, an ion-flux independent increase of the intracellular concentration of Ca²⁺ ([Ca²⁺]_i), but not of [K⁺]_i or [Na⁺]_i, and the alkalization of the cytosol. The combination of all three processes is obligatory to trigger flagellar beating. However, the time-course monitoring of sperm motion kinetics and changes in the [Ca²⁺]_i, [K⁺]_i and [Na⁺]_i in SW or in non-ionic activation media, showed that the post activated maintenance of spermatozoa motility is dependent on extracellular Ca²⁺ and K⁺. A meta-analysis of a seabream sperm transcriptome uncovered the expression of multiple ion channels, some of which were immunolocalized in the head and/or tail of the spermatozoon. Selective pharmacological inhibition of these ion channel families impaired the long-term motility, progressivity, and velocity of SW-activated spermatozoa. The data further revealed that some antagonists of K⁺-selective or Ca²⁺-selective channels, as well as of stretch-activated and mechanosensitive channels, altered the trajectory of spermatozoa, suggesting that these ion channels are likely involved in the control of the swimming pattern of the post activated spermatozoon. These combined findings provide new insight into the signaling pathways regulating spermatozoon activation and swimming performance in marine fishes. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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19 pages, 4735 KiB

Open AccessArticle

Elevated and Sustained Intracellular Calcium Signalling Is Necessary for Efficacious Induction of the Human Sperm Acrosome Reaction

by Priyanka Prajapati, Shruti Kane, Rachel C. McBrinn, Morven S. Dean, Sarah J. Martins da Silva and Sean G. Brown

Int. J. Mol. Sci. 2022, 23(19), 11253; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911253 - 24 Sep 2022

Cited by 5 | Viewed by 2425

Abstract

Progesterone and prostaglandin E1 are postulated to trigger the human sperm acrosome reaction (AR). However, their reported efficacy is very variable which likely, in part, reflects the plethora of experimental conditions and methodologies used to detect this physiologically relevant event. The purpose of this study was to develop an assay for the robust induction and objective measurement of the complete AR. Sperm from healthy volunteers or patients undertaking IVF were treated with a variety of ligands (progesterone, prostaglandin E1 or NH₄Cl, alone or in combinations). AR, motility and intracellular calcium measurements were measured using flow cytometry, computer-assisted sperm analysis (CASA) and fluorimetry, respectively. The AR was significantly increased by the simultaneous application of progesterone, prostaglandin E1 and NH₄Cl, following an elevated and sustained intracellular calcium concentration. However, we observed notable inter- and intra-donor sample heterogeneity of the AR induction. When studying the patient samples, we found no relationship between the IVF fertilization rate and the AR. We conclude that progesterone and prostaglandin E1 alone do not significantly increase the percentage of live acrosome-reacted sperm. This assay has utility for drug discovery and sperm toxicology studies but is not predictive for IVF success. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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21 pages, 3104 KiB

Open AccessArticle

cAMP and the Fibrous Sheath Protein CABYR (Ca²⁺-Binding Tyrosine-Phosphorylation-Regulated Protein) Is Required for 4D Sperm Movement

by Linda Frintrop, Caroline Wiesehöfer, Aura Stoskus, Gero Hilken, Marko Dubicanac, Nicola Edith von Ostau, Sebastian Rode, Jens Elgeti, Jaroslaw Thomas Dankert and Gunther Wennemuth

Int. J. Mol. Sci. 2022, 23(18), 10607; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810607 - 13 Sep 2022

Cited by 1 | Viewed by 1522

Abstract

A new life starts with successful fertilization whereby one sperm from a pool of millions fertilizes the oocyte. Sperm motility is one key factor for this selection process, which depends on a coordinated flagellar movement. The flagellar beat cycle is regulated by Ca²⁺ entry via CatSper, cAMP, Mg²⁺, ADP and ATP. This study characterizes the effects of these parameters for 4D sperm motility, especially for flagellar movement and the conserved clockwise (CW) path chirality of murine sperm. Therefore, we use detergent-extracted mouse sperm and digital holographic microscopy (DHM) to show that a balanced ratio of ATP to Mg²⁺ in addition with 18 µM cAMP and 1 mM ADP is necessary for controlled flagellar movement, induction of rolling along the long axis and CW path chirality. Rolling along the sperm’s long axis, a proposed mechanism for sperm selection, is absent in sea urchin sperm, lacking flagellar fibrous sheath (FS) and outer-dense fibers (ODFs). In sperm lacking CABYR, a Ca²⁺-binding tyrosine-phosphorylation regulated protein located in the FS, the swim path chirality is preserved. We conclude that specific concentrations of ATP, ADP, cAMP and Mg²⁺ as well as a functional CABYR play an important role for sperm motility especially for path chirality. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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17 pages, 3190 KiB

Open AccessArticle

Membrane-Bound EMC10 Is Required for Sperm Motility via Maintaining the Homeostasis of Cytoplasm Sodium in Sperm

by Lijie Liu, Shanhua Mao, Kuangyang Chen, Jiarong Dai, Shuoshuo Jin, Lijiao Chen, Yahao Wang, Lina Guo, Yiting Yang, Chongwen Zhan, Zuquan Xiong, Hua Diao, Yuchuan Zhou, Qiang Ding and Xuanchun Wang

Int. J. Mol. Sci. 2022, 23(17), 10069; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710069 - 03 Sep 2022

Cited by 2 | Viewed by 1448

Abstract

Endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is an evolutionarily conserved and multifunctional factor across species. We previously reported that Emc10 knockout (KO) leads to mouse male infertility. Emc10-null spermatozoa exhibit multiple aspects of dysfunction, including reduced sperm motility. Two subunits of a Na/K-ATPase, ATP1A4 and ATP1B3, are nearly absent in Emc10 KO spermatozoa. Here, two isoforms of EMC10 were characterized in the mouse testis and epididymis: the membrane-bound (mEMC10) and secreted (scEMC10) isoforms. We present evidence that mEMC10, rather than scEMC10, is required for cytoplasm sodium homeostasis by positively regulating ATP1B3 expression in germ cells. Intra-testis mEMC10 overexpression rescued the sperm motility defect caused by Emc10 KO, while exogenous recombinant scEMC10 protein could not improve the motility of spermatozoa from either Emc10 KO mouse or asthenospermic subjects. Clinically, there is a positive association between ATP1B3 and EMC10 protein levels in human spermatozoa, whereas no correlation was proven between seminal plasma scEMC10 levels and sperm motility. These results highlight the important role of the membrane-bound EMC10 isoform in maintaining cytoplasm sodium homeostasis and sperm motility. Based on the present results, the mEMC10-Na, K/ATPase α4β3 axis is proposed as a novel mechanism underlying the regulation of cytoplasmic sodium and sperm motility, and its components seem to have therapeutic potential for asthenospermia. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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19 pages, 5285 KiB

Open AccessArticle

Down Regulation of Catsper1 Expression by Calmodulin Inhibitor (Calmidazolium): Possible Implications for Fertility

by Angela Forero-Forero, Stephany López-Ramírez, Ricardo Felix, Javier Hernández-Sánchez, Emiliano Tesoro-Cruz, Sandra Orozco-Suárez, Janet Murbartián, Elizabeth Soria-Castro, Aleida Olivares, Carolina Bekker-Méndez, Vladimir Paredes-Cervantes and Norma Oviedo

Int. J. Mol. Sci. 2022, 23(15), 8070; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158070 - 22 Jul 2022

Cited by 3 | Viewed by 1804

Abstract

The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. Catsper1 expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the Catsper1 promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the Casper genes, and the motility and fertility of the sperm. Catsper1 promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the Catsper1 promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of Catsper1, as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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18 pages, 3971 KiB

Open AccessArticle

The Non-Gastric H⁺/K⁺ ATPase (ATP12A) Is Expressed in Mammalian Spermatozoa

by Maria Favia, Andrea Gerbino, Elisabetta Notario, Vincenzo Tragni, Maria Noemi Sgobba, Maria Elena Dell’Aquila, Ciro Leonardo Pierri, Lorenzo Guerra and Elena Ciani

Int. J. Mol. Sci. 2022, 23(3), 1048; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031048 - 19 Jan 2022

Cited by 2 | Viewed by 2216

Abstract

H⁺/K⁺ ATPase Type 2 is an heteromeric membrane protein involved in cation transmembrane transport and consists of two subunits: a specific α subunit (ATP12A) and a non-specific β subunit. The aim of this study was to demonstrate the presence and establish the localization of ATP12A in spermatozoa from Bubalus bubalis, Bos taurus and Ovis aries. Immunoblotting revealed, in all three species, a major band (100 kDa) corresponding to the expected molecular mass. The ATP12A immunolocalization pattern showed, consistently in the three species, a strong signal at the acrosome. These results, described here for the first time in spermatozoa, are consistent with those observed for the β₁ subunit of Na⁺/K⁺ ATPase, suggesting that the latter may assemble with the α subunit to produce a functional ATP12A dimer in sperm cells. The above scenario appeared to be nicely supported by 3D comparative modeling and interaction energy calculations. The expression of ATP12A during different stages of bovine sperm maturation progressively increased, moving from epididymis to deferent ducts. Based on overall results, we hypothesize that ATP12A may play a role in acrosome reactions. Further studies will be required in order to address the functional role of this target protein in sperm physiology. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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20 pages, 5169 KiB

Open AccessArticle

Blocking NHE Channels Reduces the Ability of In Vitro Capacitated Mammalian Sperm to Respond to Progesterone Stimulus

by Marc Yeste, Sandra Recuero, Carolina Maside, Albert Salas-Huetos, Sergi Bonet and Elisabeth Pinart

Int. J. Mol. Sci. 2021, 22(23), 12646; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312646 - 23 Nov 2021

Cited by 12 | Viewed by 2091

Abstract

Few data exist about the presence and physiological role of Na+/H+ exchangers (NHEs) in the plasma membrane of mammalian sperm. In addition, the involvement of these channels in the ability of sperm to undergo capacitation and acrosomal reaction has not been investigated in any mammalian species. In the present study, we addressed whether these channels are implicated in these two sperm events using the pig as a model. We also confirmed the presence of NHE1 channels in the plasma membrane of ejaculated sperm by immunofluorescence and immunoblotting. The function of NHE channels during in vitro capacitation was analyzed by incubating sperm samples in capacitating medium for 300 min in the absence or presence of a specific blocker (DMA; 5-(N,N-dimethyl)-amiloride) at different concentrations (1, 5, and 10 µM); acrosome exocytosis was triggered by adding progesterone after 240 min of incubation. Sperm motility and kinematics, integrity of plasma and acrosome membranes, membrane lipid disorder, intracellular calcium and reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were evaluated after 0, 60, 120, 180, 240, 250, 270, and 300 min of incubation. NHE1 localized in the connecting and terminal pieces of the flagellum and in the equatorial region of the sperm head and was found to have a molecular weight of 75 kDa. During the first 240 min of incubation, i.e., before the addition of progesterone, blocked and control samples did not differ significantly in any of the parameters analyzed. However, from 250 min of incubation, samples treated with DMA showed significant alterations in total motility and the amplitude of lateral head displacement (ALH), acrosomal integrity, membrane lipid disorder, and MMP. In conclusion, while NHE channels are not involved in the sperm ability to undergo capacitation, they could be essential for triggering acrosome exocytosis and hypermotility after progesterone stimulus. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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27 pages, 5119 KiB

Open AccessArticle

Sperm Methylome Profiling Can Discern Fertility Levels in the Porcine Biomedical Model

by Fabio Pértille, Manuel Alvarez-Rodriguez, Arthur Nery da Silva, Isabel Barranco, Jordi Roca, Carlos Guerrero-Bosagna and Heriberto Rodriguez-Martinez

Int. J. Mol. Sci. 2021, 22(5), 2679; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052679 - 06 Mar 2021

Cited by 14 | Viewed by 3591

Abstract

A combined Genotyping By Sequencing (GBS) and methylated DNA immunoprecipitation (MeDIP) protocol was used to identify—in parallel—genetic variation (Genomic-Wide Association Studies (GWAS) and epigenetic differences of Differentially Methylated Regions (DMR) in the genome of spermatozoa from the porcine animal model. Breeding boars with good semen quality (n = 11) and specific and well-documented differences in fertility (farrowing rate, FR) and prolificacy (litter size, LS) (n = 7) in artificial insemination programs, using combined FR and LS, were categorized as High Fertile (HF, n = 4) or Low Fertile (LF, n = 3), and boars with Unknown Fertility (UF, n = 4) were tested for eventual epigenetical similarity with those fertility-proven. We identified 165,944 Single Nucleotide Polymorphisms (SNPs) that explained 14–15% of variance among selection lines. Between HF and LF individuals (n = 7, 4 HF and 3 LF), we identified 169 SNPs with p ≤ 0.00015, which explained 58% of the variance. For the epigenetic analyses, we considered fertility and period of ejaculate collection (late-summer and mid-autumn). Approximately three times more DMRs were observed in HF than in LF boars across these periods. Interestingly, UF boars were clearly clustered with one of the other HF or LF groups. The highest differences in DMRs between HF and LF experimental groups across the pig genome were located in the chr 3, 9, 13, and 16, with most DMRs being hypermethylated in LF boars. In both HF and LF boars, DMRs were mostly hypermethylated in late-summer compared to mid-autumn. Three overlaps were detected between SNPs (p ≤ 0.0005, n = 1318) and CpG sites within DMRs. In conclusion, fertility levels in breeding males including FR and LS can be discerned using methylome analyses. The findings in this biomedical animal model ought to be applied besides sire selection for andrological diagnosis of idiopathic sub/infertility. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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Review

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17 pages, 829 KiB

Open AccessReview

Testis-Specific Isoform of Na⁺-K⁺ ATPase and Regulation of Bull Fertility

by Saurabh Tiwari, Gayathri Rajamanickam, Veena Unnikrishnan, Mina Ojaghi, John P. Kastelic and Jacob C. Thundathil

Int. J. Mol. Sci. 2022, 23(14), 7936; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147936 - 19 Jul 2022

Cited by 6 | Viewed by 2530

Abstract

An advanced understanding of sperm function is relevant for evidence-based male fertility prediction and addressing male infertility. A standard breeding soundness evaluation (BSE) merely identifies gross abnormalities in bulls, whereas selection based on single nucleotide polymorphisms and genomic estimated breeding values overlooks sub-microscopic differences in sperm. Molecular tools are important for validating genomic selection and advancing knowledge on the regulation of male fertility at an interdisciplinary level. Therefore, research in this field is now focused on developing a combination of in vitro sperm function tests and identifying biomarkers such as sperm proteins with critical roles in fertility. The Na⁺-K⁺ ATPase is a ubiquitous transmembrane protein and its α4 isoform (ATP1A4) is exclusively expressed in germ cells and sperm. Furthermore, ATP1A4 is essential for male fertility, as it interacts with signaling molecules in both raft and non-raft fractions of the sperm plasma membrane to regulate capacitation-associated signaling, hyperactivation, sperm-oocyte interactions, and activation. Interestingly, ATP1A4 activity and expression increase during capacitation, challenging the widely accepted dogma of sperm translational quiescence. This review discusses the literature on the role of ATP1A4 during capacitation and fertilization events and its prospective use in improving male fertility prediction. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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20 pages, 2780 KiB

Open AccessReview

A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals

by Ariadna Delgado-Bermúdez, Marc Yeste, Sergi Bonet and Elisabeth Pinart

Int. J. Mol. Sci. 2022, 23(11), 6333; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116333 - 06 Jun 2022

Cited by 9 | Viewed by 2798

Abstract

Alkalinization of sperm cytosol is essential for plasma membrane hyperpolarization, hyperactivation of motility, and acrosomal exocytosis during sperm capacitation in mammals. The plasma membrane of sperm cells contains different ion channels implicated in the increase of internal pH (pH_i) by favoring either bicarbonate entrance or proton efflux. Bicarbonate transporters belong to the solute carrier families 4 (SLC4) and 26 (SLC26) and are currently grouped into Na⁺/HCO₃⁻ transporters and Cl⁻/HCO₃⁻ exchangers. Na⁺/HCO₃⁻ transporters are reported to be essential for the initial and fast entrance of HCO₃⁻ that triggers sperm capacitation, whereas Cl⁻/HCO₃⁻ exchangers are responsible for the sustained HCO₃⁻ entrance which orchestrates the sequence of changes associated with sperm capacitation. Proton efflux is required for the fast alkalinization of capacitated sperm cells and the activation of pH-dependent proteins; according to the species, this transport can be mediated by Na⁺/H⁺ exchangers (NHE) belonging to the SLC9 family and/or voltage-gated proton channels (HVCN1). Herein, we discuss the involvement of each of these channels in sperm capacitation and the acrosome reaction. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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28 pages, 864 KiB

Open AccessReview

Sperm Ion Transporters and Channels in Human Asthenozoospermia: Genetic Etiology, Lessons from Animal Models, and Clinical Perspectives

by Emma Cavarocchi, Marjorie Whitfield, Fabrice Saez and Aminata Touré

Int. J. Mol. Sci. 2022, 23(7), 3926; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073926 - 01 Apr 2022

Cited by 11 | Viewed by 3264

Abstract

In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle that provides the mechanical force for sperm propulsion and motility. Importantly several functional maturation events that occur during the journey of the sperm cells through the genital tracts are necessary for the activation of flagellar beating and the acquisition of fertilization potential. Ion transporters and channels located at the surface of the sperm cells have been demonstrated to be involved in these processes, in particular, through the activation of downstream signaling pathways and the promotion of novel biochemical and electrophysiological properties in the sperm cells. We performed a systematic literature review to describe the currently known genetic alterations in humans that affect sperm ion transporters and channels and result in asthenozoospermia, a pathophysiological condition defined by reduced or absent sperm motility and observed in nearly 80% of infertile men. We also present the physiological relevance and functional mechanisms of additional ion channels identified in the mouse. Finally, considering the state-of-the art, we discuss future perspectives in terms of therapeutics of asthenozoospermia and male contraception. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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24 pages, 2344 KiB

Open AccessReview

Structure and Function of Ion Channels Regulating Sperm Motility—An Overview

by Karolina Nowicka-Bauer and Monika Szymczak-Cendlak

Int. J. Mol. Sci. 2021, 22(6), 3259; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063259 - 23 Mar 2021

Cited by 42 | Viewed by 4493

Abstract

Sperm motility is linked to the activation of signaling pathways that trigger movement. These pathways are mainly dependent on Ca²⁺, which acts as a secondary messenger. The maintenance of adequate Ca²⁺ concentrations is possible thanks to proper concentrations of other ions, such as K⁺ and Na⁺, among others, that modulate plasma membrane potential and the intracellular pH. Like in every cell, ion homeostasis in spermatozoa is ensured by a vast spectrum of ion channels supported by the work of ion pumps and transporters. To achieve success in fertilization, sperm ion channels have to be sensitive to various external and internal factors. This sensitivity is provided by specific channel structures. In addition, novel sperm-specific channels or isoforms have been found with compositions that increase the chance of fertilization. Notably, the most significant sperm ion channel is the cation channel of sperm (CatSper), which is a sperm-specific Ca²⁺ channel required for the hyperactivation of sperm motility. The role of other ion channels in the spermatozoa, such as voltage-gated Ca²⁺ channels (VGCCs), Ca²⁺-activated Cl-channels (CaCCs), SLO K⁺ channels or voltage-gated H⁺ channels (VGHCs), is to ensure the activation and modulation of CatSper. As the activation of sperm motility differs among metazoa, different ion channels may participate; however, knowledge regarding these channels is still scarce. In the present review, the roles and structures of the most important known ion channels are described in regard to regulation of sperm motility in animals. Full article

(This article belongs to the Special Issue Ion Channels in Sperm Physiology 2.0)

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