Two‐pore channel 1 and Ca2+ release‐activated Ca2+ channels contribute to the acrosomal pH‐dependent intracellular Ca2+ increase in mouse sperm

Oliver, Elizabeth; Jabloñski, Martina; Buffone, Mariano G.; Darszon, Alberto

doi:10.1113/jp284247

Cited by 3 publications

(7 citation statements)

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“…It is known that, as in the endoplasmic reticulum (ER), organelles such as lysosomes, lysosome-related organelles, secretory vesicles, vacuoles, and acidocalcisomes express Ca 2+ -permeable channels that can participate in intracellular signaling processes. These include members of the transient receptor (TRP) ion channel family, two-pore channels (TPC), ATP-activated ionotropic receptors (P2X), inositol triphosphate (IP3), and ryanodine (Ryr) receptors [161,162]. In mammalian sperm, acrosomal Ca 2+ concentration is regulated by the IP3R and ryanodine receptors [163], the sarco/endoplasmic reticulum Ca 2+− ATPases (SERCA) [164], and the two-pore channel 1 (TPC1) [162,165].…”

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

“…These include members of the transient receptor (TRP) ion channel family, two-pore channels (TPC), ATP-activated ionotropic receptors (P2X), inositol triphosphate (IP3), and ryanodine (Ryr) receptors [161,162]. In mammalian sperm, acrosomal Ca 2+ concentration is regulated by the IP3R and ryanodine receptors [163], the sarco/endoplasmic reticulum Ca 2+− ATPases (SERCA) [164], and the two-pore channel 1 (TPC1) [162,165]. TPC1 channels participate in the acrosomal Ca 2+ release regulated by pHa [162].…”

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

“…In mammalian sperm, acrosomal Ca 2+ concentration is regulated by the IP3R and ryanodine receptors [163], the sarco/endoplasmic reticulum Ca 2+− ATPases (SERCA) [164], and the two-pore channel 1 (TPC1) [162,165]. TPC1 channels participate in the acrosomal Ca 2+ release regulated by pHa [162].…”

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

“…In mice and human sperm, acrosomal alkalinization elevates [Ca 2+ ]i and triggers AR [166]. At least in mouse sperm, pHa alkalinization is important for acrosomal Ca 2+ efflux and extracellular Ca 2+ influx during AR [162].…”

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

“…Recently, it was demonstrated that pHa alkalinization stimulates TPC1 channels that mediate acrosomal Ca 2+ release and that the osmotic component plays a minor role in this response. In turn, acrosomal Ca 2+ efflux would activate plasma membrane Ca 2+ CRAC-type channels to favor the AR process [162]. pHa may serve as a marker of capacitation status, reflecting sperm readiness to respond to fertilization triggers.…”

Section: Role Of Pha During Sperm Mammalian Capacitationmentioning

confidence: 99%

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Cytosolic and Acrosomal pH Regulation in Mammalian Sperm

Chávez,

Carrasquel-Martínez,

Hernández-Garduño

et al. 2024

Cells

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As in most cells, intracellular pH regulation is fundamental for sperm physiology. Key sperm functions like swimming, maturation, and a unique exocytotic process, the acrosome reaction, necessary for gamete fusion, are deeply influenced by pH. Sperm pH regulation, both intracellularly and within organelles such as the acrosome, requires a coordinated interplay of various transporters and channels, ensuring that this cell is primed for fertilization. Consistent with the pivotal importance of pH regulation in mammalian sperm physiology, several of its unique transporters are dependent on cytosolic pH. Examples include the Ca2+ channel CatSper and the K+ channel Slo3. The absence of these channels leads to male infertility. This review outlines the main transport elements involved in pH regulation, including cytosolic and acrosomal pH, that participate in these complex functions. We present a glimpse of how these transporters are regulated and how distinct sets of them are orchestrated to allow sperm to fertilize the egg. Much research is needed to begin to envision the complete set of players and the choreography of how cytosolic and organellar pH are regulated in each sperm function.

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Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

Section: Role Of [Ca 2+ ]I In Pha Regulationmentioning

confidence: 99%

Section: Role Of Pha During Sperm Mammalian Capacitationmentioning

confidence: 99%

See 3 more Smart Citations

Cytosolic and Acrosomal pH Regulation in Mammalian Sperm

Chávez,

Carrasquel-Martínez,

Hernández-Garduño

et al. 2024

Cells

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Molecular mechanisms of mammalian sperm capacitation, and its regulation by sodium‐dependent secondary active transporters

Takei

2024

Reprod Medicine & Biology

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BackgroundMammalian spermatozoa have to be “capacitated” to be fertilization‐competent. Capacitation is a collective term for the physiological and biochemical changes in spermatozoa that occur within the female body. However, the regulatory mechanisms underlying capacitation have not been fully elucidated.MethodsPreviously published papers on capacitation, especially from the perspective of ions/channels/transporters, were extracted and summarized.ResultsCapacitation can be divided into two processes: earlier events (membrane potential hyperpolarization, intracellular pH rise, intracellular Ca2+ rise, etc.) and two major later events: hyperactivation and the acrosome reaction. Earlier events are closely interconnected with each other. Various channels/transporters are involved in the regulation of them, which ultimately lead to the later events. Manipulating the extracellular K+ concentration based on the oviductal concentration modifies membrane potential; however, the later events and fertilization are not affected, suggesting the uninvolvement of membrane potential in capacitation. Hyperpolarization is a highly conserved phenomenon among mammalian species, indicating its importance in capacitation. Therefore, the physiological importance of hyperpolarization apart from membrane potential is suggested.ConclusionThe hypotheses are (1) hyperpolarizing Na+ dynamics (decrease in intracellular Na+) and Na+‐driven secondary active transporters play a vital role in capacitation and (2) the sperm‐specific potassium channel Slo3 is involved in volume and/or morphological regulation.

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Flagellar pH homeostasis mediated by Na+/H+ exchangers regulates human sperm functions through coupling with CatSper and KSper activation

Liang,

Ji,

Song

et al. 2024

Human Reproduction

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STUDY QUESTION Whether and how do Na+/H+ exchangers (NHEs) regulate the physiological functions of human sperm? SUMMARY ANSWER NHE-mediated flagellar intracellular pH (pHi) homeostasis facilitates the activation of the pH-sensitive, sperm-specific Ca2+ channel (CatSper) and the sperm-specific K+ channel (KSper), which subsequently modulate sperm motility, hyperactivation, flagellar tyrosine phosphorylation, and the progesterone (P4)-induced acrosome reaction. WHAT IS KNOWN ALREADY Sperm pHi alkalization is an essential prerequisite for the acquisition of sperm-fertilizing capacity. Different sperm functions are strictly controlled by particular pHi regulatory mechanisms. NHEs are suggested to modulate sperm H+ efflux. STUDY DESIGN, SIZE, DURATION This was a laboratory study that used samples from >50 sperm donors over a period of 1 year. To evaluate NHE action on human sperm function, 5-(N,N-dimethyl)-amiloride (DMA), a highly selective inhibitor of NHEs, was utilized. All experiments were repeated at least five times using different individual sperm samples or cells. PARTICIPANTS/MATERIALS, SETTING, METHODS By utilizing the pH fluorescent indicator pHrodo Red-AM, we detected alterations in single-cell pHi value in human sperm. The currents of CatSper and KSper in human sperm were recorded by the whole-cell patch-clamp technique. Changes in population and single-cell Ca2+ concentrations ([Ca2+]i) of human sperm loaded with Fluo 4-AM were measured. Membrane potential (Vm) and population pHi were quantitatively examined by a multimode plate reader after sperm were loaded with 3,3′-dipropylthiadicarbocyanine iodide and 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester, respectively. Sperm motility parameters were assessed by a computer-assisted semen analysis system. Tyrosine phosphorylation was determined by immunofluorescence, and sperm acrosome reaction was evaluated by Pisum sativum agglutinin-FITC staining. MAIN RESULTS AND THE ROLE OF CHANCE DMA-induced NHEs inhibition severely acidified the human sperm flagellar pHi from 7.20 ± 0.04 to 6.38 ± 0.12 (mean ± SEM), while the effect of DMA on acrosomal pHi was less obvious (from 5.90 ± 0.13 to 5.57 ± 0.12, mean ± SEM). The whole-cell patch-clamp recordings revealed that NHE inhibition remarkably suppressed alkalization-induced activation of CatSper and KSper. As a consequence, impairment of [Ca2+]i homeostasis and Vm maintenance were detected in the presence of DMA. During the capacitation process, pre-treatment with DMA for 2 h potently decreased sperm pHi, which in turn decreased sperm motility and kinetic parameters. Sperm capacitation-associated functions, including hyperactivation, tyrosine phosphorylation, and P4-induced acrosome reaction, were also compromised by NHE inhibition. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION This was an in vitro study. Caution should be taken when extrapolating these results to in vivo applications. WIDER IMPLICATIONS OF THE FINDINGS This study revealed that NHEs are important physiological regulators for human CatSper and KSper, which are indispensable for human sperm fertility, suggesting that malfunction of NHEs could be an underlying mechanism for the pathogenesis of male infertility. FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (32271167 and 81871202 to X.Z.), Jiangsu Innovation and Entrepreneurship Talent Plan (JSSCRC20211543 to X.Z.), the Social Development Project of Jiangsu Province (No. BE2022765 to X.Z.), the Society and livelihood Project of Nantong City (No. MS22022087 to X.Z.), and the Natural Science Foundation of Jiangsu Province (BK20220608 to H.K.). The authors have no competing interests to declare.

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Two‐pore channel 1 and Ca²⁺ release‐activated Ca²⁺ channels contribute to the acrosomal pH‐dependent intracellular Ca²⁺ increase in mouse sperm

Abstract: support-information-section).

Cited by 3 publications

References 59 publications

Cytosolic and Acrosomal pH Regulation in Mammalian Sperm

Cytosolic and Acrosomal pH Regulation in Mammalian Sperm

Molecular mechanisms of mammalian sperm capacitation, and its regulation by sodium‐dependent secondary active transporters

Flagellar pH homeostasis mediated by Na+/H+ exchangers regulates human sperm functions through coupling with CatSper and KSper activation

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