参与调节哺乳动物精子运动的离子通道研究进展

doi:10.11843/j.issn.0366-6964.2023.07.005

摘要/Abstract

摘要： 精子运动能力是精子完成自然受精、实现自然条件下精子-卵母细胞融合的必要条件。精子从雄性附睾经生殖道进入雌性生殖道的过程中，其运动形式可以在很短的时间内根据环境的变化而做出改变，表明精子膜蛋白（离子通道）参与精子运动的调节，离子通道的正常表达和受精过程密切相关。目前研究发现Ca²⁺、K⁺、Na⁺等离子通道均参与精子膜极化、运动、获能和顶体反应等生理过程，且通过膜片钳和电生理学等技术初步了解精子离子通道的作用分子机制和拓扑结构。本文就参与调节精子运动的Ca²⁺、pH、电压门控Na⁺、K⁺、Cl^-通道的生理功能和拓扑结构进行了总结，期望能为精子离子通道的调节机制和功能研究提供全面的信息，促进动物生殖生物学的发展。

关键词: 精子, 离子通道, 精子运动, Ca²⁺/K⁺, 拓扑结构

Abstract: Sperm motility is a necessary condition for natural fertilization and achieving sperm-oocyte fusion under natural conditions. Sperm exhibit different motility patterns during the passage from the male epididymis to the female reproductive tract, which could be altered within a short period of time depending on changes in the environment, demonstrating that the sperm membrane proteins (ion channels) are involved in the regulation of sperm motility, and the normal expression of ion channels is closely related to the process of fertilization. Current studies have found that Ca²⁺, K⁺ and Na⁺ plasma channels are involved in physiological processes such as sperm membrane polarization, movement, capacitation and acrosomal reaction. The molecular mechanism and topological structure of sperm ion channels are preliminary understood through patch clamp and electrophysiology techniques. The physiological functions and topological structures of Ca²⁺, pH, voltage-gated Na⁺, K⁺, Cl^- channels involved in the regulation of sperm motility were summarized in this paper, in the hope of providing the comprehensive information on regulating mechanism and function of ion channel research, and promoting the development of animal reproductive biology.

Key words: sperm, ion channels, sperm motility, Ca²⁺/K⁺, topological structure

中图分类号:

S814

何琪富, 高峰, 吴盛辉, 张涌, 权富生. 参与调节哺乳动物精子运动的离子通道研究进展[J]. 畜牧兽医学报, 2023, 54(7): 2708-2722.

HE Qifu, GAO Feng, WU Shenghui, ZHANG Yong, QUAN Fusheng. Advances in Ion Channels Involved in the Regulation of Mammalian Sperm Motility[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2708-2722.

参考文献 122

[1]	JAMES E R, CARRELL D T, ASTON K I, et al.The role of the epididymis and the contribution of epididymosomes to mammalian reproduction[J].Int J Mol Sci, 2020, 21(15):5377.
[2]	林秋敏, 赖宝色.精子运动性能对精子质量影响的研究进展[J].畜禽业, 2022, 33(9):1-5.LIN Q M, LAI B S.Research progress on the effect of sperm motility on sperm quality[J].Livestock and Poultry Industry, 2022, 33(9):1-5.(in Chinese)
[3]	BOCKLANDT S, VILAIN E.Sex differences in brain and behavior:Hormones versus genes[J].Adv Genet, 2007, 59:245-266.
[4]	宋平平, 邹沙沙, 李铮, 等.精子鞭毛结构蛋白研究进展[J].上海交通大学学报:医学版, 2015, 35(9):1384-1388.SONG P P, ZOU S S, LI Z, et al.Research advances of structural proteins of sperm flagella[J].Journal of Shanghai Jiaotong University:Medical Science, 2015, 35(9):1384-1388.(in Chinese)
[5]	BERNARDINO R L, CARRAGETA D F, SOUSA M, et al.pH and male fertility:Making sense on pH homeodynamics throughout the male reproductive tract[J].Cell Mol Life Sci, 2019, 76(19):3783-3800.
[6]	贺亚南, 朱化彬, 陈晓丽, 等.哺乳动物精子获能前后的理化变化及获能机制研究进展[J].畜牧兽医学报, 2013, 44(12):1867-1873.HE Y N, ZHU H B, CHEN X L, et al.Advance of capacitation mechanism and the physiochemical changes of sperm before and after capacitation of mammalian[J].Acta Veterinaria et Zootechnica Sinica, 2013, 44(12):1867-1873.(in Chinese)
[7]	CAVAROCCHI E, WHITFIELD M, SAEZ F, et al.Sperm ion transporters and channels in human asthenozoospermia:Genetic etiology, lessons from animal models, and clinical perspectives[J].Int J Mol Sci, 2022, 23(7):3926.
[8]	TEVES M E, GUIDOBALDI H A, UÑATES D R, et al.Molecular mechanism for human sperm chemotaxis mediated by progesterone[J].PLoS One, 2009, 4(12):e8211.
[9]	KIRICHOK Y, LISHKO P V.Rediscovering sperm ion channels with the patch-clamp technique[J].Mol Hum Reprod, 2011, 17(8):478-499.
[10]	BRUKMAN N G, NUÑEZ S Y, DEL CARMEN PUGA MOLINA L, et al.Tyrosine phosphorylation signaling regulates Ca2+ entry by affecting intracellular pH during human sperm capacitation[J].J Cell Physiol, 2019, 234(4):5276-5288.
[11]	MAHAJAN A, SHARMA P, MISHRA A K, et al.Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction[J].J Cell Physiol, 2022, 237(7):2888-2912.
[12]	姚叶洁, 高怡宁, 金君, 等.精子尾部离子通道KSper和CatSper的结构与功能[J].国际生殖健康/计划生育杂志, 2020, 39(2):147-152.YAO Y J, GAO Y N, JIN J, et al.The structure and function of ion channels KSper and CatSper in sperm tail[J].Journal of International Reproductive Health/Family Planning, 2020, 39(2):147-152.(in Chinese)
[13]	CAROPPO E.Understanding sperm motility regulation:It's a long road ahead[J].Fertil Steril, 2021, 115(2):311-312.
[14]	苑洋洋.精子特异性离子通道的生理与毒理作用研究[D].南昌:南昌大学, 2020:1-92.YUAN Y Y.Studies on physiological and toxicological effects of sperm-specific ion channels[D].Nanchang:Nanchang University, 2020:1-92.(in Chinese)
[15]	GERVASI M G, VISCONTI P E.Molecular changes and signaling events occurring in spermatozoa during epididymal maturation[J].Andrology, 2017, 5(2):204-218.
[16]	FREITAS M J, VIJAYARAGHAVAN S, FARDILHA M.Signaling mechanisms in mammalian sperm motility[J].Biol Reprod, 2017, 96(1):2-12.
[17]	ORTA G, FERREIRA G, JOSÉ O, et al.Human spermatozoa possess a calcium-dependent chloride channel that may participate in the acrosomal reaction[J].J Physiol, 2012, 590(11):2659-2675.
[18]	胡启蒙.哺乳动物精子超激活运动研究进展[J].生命科学, 2017, 29(11):1185-1191.HU Q M.Research progress of hyperactivation of mammalian sperm[J].Chinese Bulletin of Life Sciences, 2017, 29(11):1185-1191.(in Chinese)
[19]	PUGA MOLINA L C, LUQUE G M, BALESTRINI P A, et al.Molecular basis of human sperm capacitation[J].Front Cell Dev Biol, 2018, 6:72.
[20]	朱振东.猪精子能量代谢的调控机理研究[D].杨凌:西北农林科技大学, 2020:1-164.ZHU Z D.Mechanisms underlying energy metabolism in boar sperm[D].Yangling:Northwest A&F University, 2020:1-164.(in Chinese)
[21]	STOREY B T.Mammalian sperm metabolism:Oxygen and sugar, friend and foe[J].Int J Dev Biol, 2008, 52(5-6):427-437.
[22]	MIKI K, QU W D, GOULDING E H, et al.Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility[J].Proc Natl Acad Sci U S A, 2004, 101(47):16501-16506.
[23]	STEEGBORN C.Structure, mechanism, and regulation of soluble adenylyl cyclases-similarities and differences to transmembrane adenylyl cyclases[J].Biochim Biophys Acta (BBA)-Mol Basis Dis, 2014, 1842(12):2535-2547.
[24]	江峰, 朱勇, 陈颖, 等.孕酮通过ABHD2受体介导的cAMP-PKA信号通路调控精子受精功能的研究[J].中国男科学杂志, 2020, 34(6):12-16.JIANG F, ZHU Y, CHEN Y, et al.Study on the progesterone regulating sperm fertilization through ABHD2 receptormediated cAMP-PKA signaling pathway[J].Chinese Journal of Andrology, 2020, 34(6):12-16.(in Chinese)
[25]	XIE F, GARCIA M A, CARLSON A E, et al.Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization[J].Dev Biol, 2006, 296(2):353-362.
[26]	LUCONI M, PORAZZI I, FERRUZZI P, et al.Tyrosine phosphorylation of the a kinase anchoring protein 3 (AKAP3) and soluble adenylate cyclase are involved in the increase of human sperm motility by bicarbonate[J].Biol Reprod, 2005, 72(1):22-32.
[27]	SHIBA K, INABA K.Distinct roles of soluble and transmembrane adenylyl cyclases in the regulation of flagellar motility in Ciona sperm[J].Int J Mol Sci, 2014, 15(8):13192-13208.
[28]	ALLOUCHE-FITOUSSI D, BREITBART H.The role of zinc in male fertility[J].Int J Mol Sci, 2020, 21(20):7796.
[29]	CORREIA J, MICHELANGELI F, PUBLICOVER S.Regulation and roles of Ca2+ stores in human sperm[J].Reproduction, 2015, 150(2):R65-R76.
[30]	康杭.精子特异性KSper和CatSper通道的调控机制和功能研究[D].南昌:南昌大学, 2020:1-94.KANG H.Study on the regulatory mechanisms and physiological functions of the sperm-specific ion channel KSper and CatSper[D].Nanchang:Nanchang University, 2020:1-94.(in Chinese)
[31]	胡庭溪, 刘霞, 孙尉峻, 等.精子动力学分析与其体内、体外受精能力的相关性[J].畜牧兽医学报, 2016, 47(8):1727-1732.HU T X, LIU X, SUN W J, et al.Correlation between sperm kinetics parameters and fertility of Holstein sex-sorted sperm in vitro and in vivo[J].Acta Veterinaria et Zootechnica Sinica, 2016, 47(8):1727-1732.(in Chinese)
[32]	COSTELLO S, MICHELANGELI F, NASH K, et al.Ca2+-stores in sperm:Their identities and functions[J].Reproduction, 2009, 138(3):425-437.
[33]	CHINOY N J, VERMA R J, PATEL K G.Effect of calcium on sperm motility of cauda epididymis in vitro[J].Acta Eur Fertil, 1983, 14(6):421-423.
[34]	ARVER S, SJÖBERG H E.Calcium fractions in seminal plasma and functional properties of human spermatozoa[J].Acta Physiol Scand, 1982, 116(2):159-165.
[35]	MARÍN-BRIGGILER C I, JHA K N, CHERTIHIN O, et al.Evidence of the presence of calcium/calmodulin-dependent protein kinase IV in human sperm and its involvement in motility regulation[J].J Cell Sci, 2005, 118(Pt 9):2013-2022.
[36]	葛婷婷, 袁露, 徐文华, 等.哺乳动物纤毛/鞭毛内运输在精子形成中的作用及机制研究进展[J].遗传, 2021, 43(11):1038-1049.GE T T, YUAN L, XU W H, et al.Role and mechanism of intraflagellar transport in mammalian spermiogenesis[J].Hereditas (Beijing), 2021, 43(11):1038-1049.(in Chinese)
[37]	SINGH A P, RAJENDER S.CatSper channel, sperm function and male fertility[J].Reprod Biomed Online, 2015, 30(1):28-38.
[38]	SUN X H, ZHU Y Y, WANG L, et al.The Catsper channel and its roles in male fertility:A systematic review[J].Reprod Biol Endocrinol, 2017, 15(1):65.
[39]	JOHNSON G P, ENGLISH A M, CRONIN S, et al.Genomic identification, expression profiling, and functional characterization of CatSper channels in the bovine[J].Biol Reprod, 2017, 97(2):302-312.
[40]	TAMBURRINO L, MARCHIANI S, MINETTI F, et al.The CatSper calcium channel in human sperm:Relation with motility and involvement in progesterone-induced acrosome reaction[J].Hum Reprod, 2014, 29(3):418-428.
[41]	KESHTGAR S, GHANBARI H, GHANI E, et al.Effect of CatSper and Hv1 channel inhibition on progesterone stimulated human sperm[J].J Reprod Infertil, 2018, 19(3):133-139.
[42]	YESTE M, LLAVANERA M, MATEO-OTERO Y, et al.HVCN1 channels are relevant for the maintenance of sperm motility during in vitro capacitation of pig spermatozoa[J].Int J Mol Sci, 2020, 21(9):3255.
[43]	CASTELLANO L E, TREVIÑO C L, RODRÍGUEZ D, et al.Transient receptor potential (TRPC) channels in human sperm:expression, cellular localization and involvement in the regulation of flagellar motility[J].FEBS Lett, 2003, 541(1-3):69-74.
[44]	GERVASI M G, OSYCKA-SALUT C, CABALLERO J, et al.Anandamide capacitates bull spermatozoa through CB1 and TRPV1 activation[J].PLoS One, 2011, 6(2):e16993.
[45]	BERNABÒ N, PISTILLI M G, MATTIOLI M, et al.Role of TRPV1 channels in boar spermatozoa acquisition of fertilizing ability[J].Mol Cell Endocrinol, 2010, 323(2):224-231.
[46]	KUMAR A, MISHRA A K, SWAIN D K, et al.Role of transient receptor potential channels in regulating spermatozoa functions:a mini-review[J].Vet World, 2018, 11(11):1618-1623.
[47]	DE BLAS G A, DARSZON A, OCAMPO A Y, et al.TRPM8, a versatile channel in human sperm[J].PLoS One, 2009, 4(6):e6095.
[48]	HAMANO K I, KAWANISHI T, MIZUNO A, et al.Involvement of transient receptor potential vanilloid (TRPV) 4 in mouse sperm thermotaxis[J].J Reprod Dev, 2016, 62(4):415-422.
[49]	SUTTON K A, JUNGNICKEL M K, FLORMAN H M.A polycystin-1 controls postcopulatory reproductive selection in mice[J].Proc Natl Acad Sci U S A, 2008, 105(25):8661-8666.
[50]	GIBBS G M, ORTA G, REDDY T, et al.Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function[J].Proc Natl Acad Sci U S A, 2011, 108(17):7034-7039.
[51]	QI H Y, MORAN M M, NAVARRO B, et al.All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility[J].Proc Natl Acad Sci U S A, 2007, 104(4):1219-1223.
[52]	BARFIELD J P, YEUNG C H, COOPER T G.Characterization of potassium channels involved in volume regulation of human spermatozoa[J].Mol Hum Reprod, 2005, 11(12):891-897.
[53]	JOSÉ O, HERNÁNDEZ-HERNÁNDEZ O, CHIRINOS M, et al.Recombinant human ZP3-induced sperm acrosome reaction:evidence for the involvement of T-and L-type voltage-gated calcium channels[J].Biochem Biophys Res Commun, 2010, 395(4):530-534.
[54]	PINTO F M, RAVINA C G, FERNÁNDEZ-SÁNCHEZ M, et al.Molecular and functional characterization of voltage-gated sodium channels in human sperm[J].Reprod Biol Endocrinol, 2009, 7:71.
[55]	CEJUDO-ROMAN A, PINTO F M, SUBIRÁN N, et al.The voltage-gated sodium channel Nav1.8 is expressed in human sperm[J].PLoS One, 2013, 8(9):e76084.
[56]	CANDENAS L, PINTO F M, CEJUDO-ROMÁN A, et al.Veratridine-sensitive Na+ channels regulate human sperm fertilization capacity[J].Life Sci, 2018, 196:48-55.
[57]	BIRCH M R, JOHANSEN M, SKAKKEBÆK N E, et al.In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel[J].Environ Int, 2022, 167:107399.
[58]	MISHRA A K, KUMAR A, YADAV S, et al.Functional insights into voltage gated proton channel (Hv1) in bull spermatozoa[J].Theriogenology, 2019, 136:118-130.
[59]	GUPTA R K, SWAIN D K, SINGH V, et al.Molecular characterization of voltage-gated potassium channel (Kv) and its importance in functional dynamics in bull spermatozoa[J].Theriogenology, 2018, 114:229-236.
[60]	CHAUHAN D S, SWAIN D K, SHAH N, et al.Functional and molecular characterization of voltage gated sodium channel Nav 1.8 in bull spermatozoa[J].Theriogenology, 2017, 90:210-218.
[61]	DARSZON A, NISHIGAKI T, BELTRAN C, et al.Calcium channels in the development, maturation, and function of spermatozoa[J].Physiol Rev, 2011, 91(4):1305-1355.
[62]	REN D J, XIA J S.Calcium signaling through CatSper channels in mammalian fertilization[J].Physiology (Bethesda), 2010, 25(3):165-175.
[63]	ORTA G, DE LA VEGA-BELTRAN J L, MARTÍN-HIDALGO D, et al.CatSper channels are regulated by protein kinase A[J].J Biol Chem, 2018, 293(43):16830-16841.
[64]	VICENTE-CARRILLO A, ÁLVAREZ-RODRÍGUEZ M, RODRÍGUEZ-MARTÍNEZ H.The CatSper channel modulates boar sperm motility during capacitation[J].Reprod Biol, 2017, 17(1):69-78.
[65]	BROWN S G, MILLER M R, LISHKO P V, et al.Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity[J].Hum Reprod, 2018, 33(10):1812-1816.
[66]	LOUX S C, CRAWFORD K R, ING N H, et al.CatSper and the relationship of hyperactivated motility to intracellular calcium and pH kinetics in equine sperm[J].Biol Reprod, 2013, 89(5):123.
[67]	KIRICHOK Y, NAVARRO B, CLAPHAM D E.Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel[J].Nature, 2006, 439(7077):737-740.
[68]	WANG D, KING S M, QUILL T A, et al.A new sperm-specific Na+/H+ exchanger required for sperm motility and fertility[J].Nat Cell Biol, 2003, 5(12):1117-1122.
[69]	LISHKO P V, BOTCHKINA I L, FEDORENKO A, et al.Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel[J].Cell, 2010, 140(3):327-337.
[70]	MARTINS A D, BERNARDINO R L, NEUHAUS-OLIVEIRA A, et al.Physiology of Na+/H+ exchangers in the male reproductive tract:Relevance for male fertility[J].Biol Reprod, 2014, 91(1):11.
[71]	BRENKER C, GOODWIN N, WEYAND I, et al.The CatSper channel:A polymodal chemosensor in human sperm[J].EMBO J, 2012, 31(7):1654-1665.
[72]	RAHBAN R, NEF S.CatSper:the complex main gate of calcium entry in mammalian spermatozoa[J].Mol Cell Endocrinol, 2020, 518:110951.
[73]	王世平, 徐光玉, 孙秀斌, 等.精子特异性钙通道CatSper1对精子线粒体呼吸与能量代谢的影响[J].现代生物医学进展, 2016, 16(27):5373-5376.WANG S P, XU G Y, SUN X B, et al.The effects of CatSper1 on mitochondrial respiration and energy metabolism in sperm[J].Progress in Modern Biomedicine, 2016, 16(27):5373-5376.(in Chinese)
[74]	NOWICKA-BAUER K, SZYMCZAK-CENDLAK M.Structure and function of ion channels regulating sperm motility-an overview[J].Int J Mol Sci, 2021, 22(6):3259.
[75]	CARLSON A E, WESTENBROEK R E, QUILL T, et al.CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm[J].Proc Natl Acad Sci U S A, 2003, 100(25):14864-14868.
[76]	CARLSON A E, QUILL T A, WESTENBROEK R E, et al.Identical phenotypes of CatSper1 and CatSper2 null sperm[J].J Biol Chem, 2005, 280(37):32238-32244.
[77]	PRAKRIYA M, LEWIS R S.Store-operated calcium channels[J].Physiol Rev, 2015, 95(4):1383-1436.
[78]	MARTIN-HIDALGO D, DE LLERA A H, CALLE-GUISADO V, et al.AMPK function in mammalian spermatozoa[J].Int J Mol Sci, 2018, 19(11):3293.
[79]	CATTERALL W A.Voltage-gated calcium channels[J].Cold Spring Harb Perspect Biol, 2011, 3(8):a003947.
[80]	REBELLO M R, MALIPHOL A B, MEDLER K F.Ryanodine receptors selectively interact with L type calcium channels in mouse taste cells[J].PLoS One, 2013, 8(6):e68174.
[81]	GARZA-LÓPEZ E, CHÁVEZ J C, SANTANA-CALVO C, et al.Cd2+ sensitivity and permeability of a low voltage-activated Ca2+ channel with CatSper-like selectivity filter[J].Cell Calcium, 2016, 60(1):41-50.
[82]	张晓柯, 王晓烔, 胡廉.温度敏感性瞬时受体电位通道调节精子功能的研究进展[J].国际生殖健康/计划生育杂志, 2016, 35(5):390-394.ZHANG X K, WANG X T, HU L.Research progress on the regulation of thermo-TRP channels on sperm function[J].Journal of International Reproductive Health/Family Planning, 2016, 35(5):390-394.(in Chinese)
[83]	CLAPHAM D E, JULIUS D, MONTELL C, et al.International union of pharmacology.XLIX.nomenclature and structure-function relationships of transient receptor potential channels[J].Pharmacol Rev, 2005, 57(4):427-450.
[84]	SENNING E N, COLLINS M D, STRATIIEVSKA A, et al.Regulation of TRPV1 ion channel by phosphoinositide (4, 5)-bisphosphate:The role of membrane asymmetry[J].J Biol Chem, 2014, 289(16):10999-11006.
[85]	KUMAR A, MAJHI R K, SWAIN N, et al.TRPV4 is endogenously expressed in vertebrate spermatozoa and regulates intracellular calcium in human sperm[J].Biochem Biophys Res Commun, 2016, 473(4):781-788.
[86]	LIU Y, WANG D K, CHEN L M.The physiology of bicarbonate transporters in mammalian reproduction[J].Biol Reprod, 2012, 86(4):99.
[87]	WENNEMUTH G, CARLSON A E, HARPER A J, et al.Bicarbonate actions on flagellar and Ca2+-channel responses:Initial events in sperm activation[J].Development, 2003, 130(7):1317-1326.
[88]	DELGADO-BERMÚDEZ A, YESTE M, BONET S, et al.A review on the role of bicarbonate and proton transporters during sperm capacitation in mammals[J].Int J Mol Sci, 2022, 23(11):6333.
[89]	PUGA MOLINA L C, PINTO N A, TORRES RODRÍGUEZ P, et al.Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human sperm capacitation[J].J Cell Physiol, 2017, 232(6):1404-1414.
[90]	杨运运, 徐计秀, 王璟琦, 等.精液液化程度与精子活力、活动率、精子密度及pH值的研究分析[J].中国医疗前沿, 2010, 5(23):66-67.YANG Y Y, XU J X, WANG J Q, et al.Degree of liquefaction of semen and sperm vitality, motility, sperm density and pH research and analysis[J].National Medical Frontiers of China, 2010, 5(23):66-67.(in Chinese)
[91]	WANG D, HU J, BOBULESCU I A, et al.A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC)[J].Proc Natl Acad Sci U S A, 2007, 104(22):9325-9330.
[92]	ZHOU J, CHEN L, LI J, et al.The semen pH affects sperm motility and capacitation[J].PLoS One, 2015, 10(7):e0132974.
[93]	BOONAMNAJ P, SOMPORNPISUT P.Insight into the role of the Hv1 C-terminal domain in dimer stabilization[J].J Phys Chem B, 2018, 122(3):1037-1048.
[94]	DECOURSEY T E.Voltage-gated proton channels and other proton transfer pathways[J].Physiol Rev, 2003, 83(2):475-579.
[95]	DECOURSEY T E.Voltage-gated proton channels:molecular biology, physiology, and pathophysiology of the HV family[J].Physiol Rev, 2013, 93(2):599-652.
[96]	QIU F, CHAMBERLIN A, WATKINS B M, et al.Molecular mechanism of Zn2+ inhibition of a voltage-gated proton channel[J].Proc Natl Acad Sci U S A, 2016, 113(40):E5962-E5971.
[97]	NISHIGAKI T, JOSÉ O, GONZÁLEZ-COTA A L, et al.Intracellular pH in sperm physiology[J].Biochem Biophys Res Commun, 2014, 450(3):1149-1158.
[98]	MISHRA A K, KUMAR A, SWAIN D K, et al.Insights into pH regulatory mechanisms in mediating spermatozoa functions[J].Vet World, 2018, 11(6):852-858.
[99]	BELTRÁN J F, BELÉN L H, LEE-ESTEVEZ M, et al.The voltage-gated T-type Ca2+ channel is key to the sperm motility of Atlantic salmon (Salmo salar)[J].Fish Physiol Biochem, 2020, 46(5):1825-1831.
[100]	GHANBARI H, KESHTGAR S, ZARE H R, et al.Inhibition of CatSper and Hv1 Channels and NOX5 enzyme affect progesterone-induced increase of intracellular calcium concentration and ROS generation in human sperm[J].Iran J Med Sci, 2019, 44(2):127-134.
[101]	MILLER M R, KENNY S J, MANNOWETZ N, et al.Asymmetrically positioned flagellar control units regulate human sperm rotation[J].Cell Rep, 2019, 26(10):2847.
[102]	LISHKO P V, KIRICHOK Y.The role of Hv1 and CatSper channels in sperm activation[J].J Physiol, 2010, 588(23):4667-4672.
[103]	NOWICKA-BAUER K, NIXON B.Molecular changes induced by oxidative stress that impair human sperm motility[J].Antioxidants (Basel), 2020, 9(2):134.
[104]	贺瑞君.Slo3通道对小鼠精子Ca2+信号作用的研究[D].南昌:南昌大学, 2013:1-76.HE R J.Studies on the role of Slo3 channel in mouse sperm Ca2+ signaling[D].Nanchang:Nanchang University, 2013:1-76.(in Chinese)
[105]	ULBRICHT W.Sodium channel inactivation:molecular determinants and modulation[J].Physiol Rev, 2005, 85(4):1271-1301.
[106]	ESCOFFIER J, KRAPF D, NAVARRETE F, et al.Flow cytometry analysis reveals a decrease in intracellular sodium during sperm capacitation[J].J Cell Sci, 2012, 125(Pt 2):473-485.
[107]	MUÑOZ-GARAY C, DE LA VEGA-BELTRÁN J L, DELGADO R, et al.Inwardly rectifying K+ channels in spermatogenic cells:Functional expression and implication in sperm capacitation[J].Dev Biol, 2001, 234(1):261-274.
[108]	ZHOU M J, YAO T C, LI J, et al.Preliminary prediction of semen quality based on modifiable lifestyle factors by using the XGBoost algorithm[J].Front Med (Lausanne), 2022, 9:811890.
[109]	ZHU X Z, XIONG Z P, ZHOU S P, et al.Analysis of reproductive damage in earthworms (Amynthas corticis) exposed to cypermethrin[J].Ecotoxicol Environ Saf, 2022, 244:114038.
[110]	QIAN X, NIMIGEAN C M, NIU X W, et al.Slo1 tail domains, but not the Ca2+ bowl, are required for the β1 subunit to increase the apparent Ca2+ sensitivity of BK channels[J].J Gen Physiol, 2002, 120(6):829-843.
[111]	DELGADO-BERMÚDEZ A, MATEO-OTERO Y, LLAVANERA M, et al.HVCN1 but not potassium channels are related to mammalian sperm cryotolerance[J].Int J Mol Sci, 2021, 22(4):1646.
[112]	GENG Y Y, FERREIRA J J, DZIKUNU V, et al.A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities[J].J Biol Chem, 2017, 292(21):8978-8987.
[113]	BRENKER C, ZHOU Y, MVLLER A, et al.The Ca2+-activated K+ current of human sperm is mediated by Slo3[J].eLife, 2014, 3:e01438.
[114]	BALLA T.Phosphoinositides:tiny lipids with giant impact on cell regulation[J].Physiol Rev, 2013, 93(3):1019-1137.
[115]	EL KHOURI E, WHITFIELD M, STOUVENEL L, et al.Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse[J].Mol Reprod Dev, 2018, 85(8-9):682-695.
[116]	YEUNG C H, BARFIELD J P, COOPER T G.Chloride channels in physiological volume regulation of human spermatozoa[J].Biol Reprod, 2005, 73(5):1057-1063.
[117]	李波, 申玉行, 邓晋超, 等.人类精子CFTR蛋白表达及其与精子活力相关性研究[J].中国男科学杂志, 2021, 35(4):17-20.LI B, SHEN Y H, DENG J C, et al.The expression of CFTR protein in human sperms and its correlation with sperm motility[J].Chinese Journal of Andrology, 2021, 35(4):17-20.(in Chinese)
[118]	CHEN W Y, XU W M, CHEN Z H, et al.Cl- is required for HCO3- entry necessary for sperm capacitation in guinea pig:involvement of a Cl-/HCO3- exchanger (SLC26A3) and CFTR[J].Biol Reprod, 2009, 80(1):115-123.
[119]	PUGA MOLINA L C, PINTO N A, TORRES N I, et al.CFTR/ENaC-dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC[J].J Biol Chem, 2018, 293(25):9924-9936.
[120]	DUAN D Y, WINTER C, COWLEY S, et al.Molecular identification of a volume-regulated chloride channel[J].Nature, 1997, 390(6658):417-421.
[121]	张杰, 刘莹, 宗志宏, 等.人精子蛋白激酶C活性及含量对其活力的影响[J].生殖与避孕, 2000, 20(3):172-176.ZHANG J, LIU Y, ZONG Z H, et al.Effects of activity and content of protein kinase C on human sperm motility[J].Reproduction & Contraception, 2000, 20(3):172-176.(in Chinese)
[122]	LIU S W, LI Y, ZOU L L, et al.Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia[J].Asian J Androl, 2017, 19(4):418-424.