Acrosome Reaction of Human Spermatozoa Is Mediated Mainly by α1H T-Type Calcium Channels

Son, Weon‐Young; Lee, J.H; Yoon, Sa‐Ryong; Lim, Joungpyo; Han, Ching-Tack

doi:10.1016/s0015-0282(00)01439-4

Cited by 9 publications

(15 citation statements)

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“…[139][140][141] However, consistent with the potential of these observations, a 1 C (L-type) channels have been detected in mammalian/ human sperm, [142][143][144][145] although it has been reported that the acrosomal response is insensitive to L-type blockers. 146,147 T-type channels are found in human sperm, and both the a 1 G and a 1 H transcripts have been reported. [147][148][149] The acrosome response is blocked by mibefradil at micromolar concentrations.…”

Section: Fertilitymentioning

confidence: 99%

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Drug Targets in the Voltage-Gated Calcium Channel Family: Why Some Are and Some Are Not

Triggle

2003

ASSAY and Drug Development Technologies

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The L-type calcium channel antagonists have been, and continue to be, a very successful group of therapeutic agents targeted at cardiovascular disorders, notably angina and hypertension. The discovery that the voltage-gated calcium channels are a large and widely distributed family with important roles in both the peripheral and central nervous systems has initiated a major search for drugs active at other calcium channel types directed at disorders of the central nervous system, including pain, epilepsy, and stroke. These efforts have not been therapeutically successful thus far, and small molecule equivalents of the L-type blockers nifedipine, diltiazem, and verapamil directed at non-L-type channels have not been found. The underlying reasons for this are discussed together with suggestions for new directions, including fertility control, oxygen-sensitive channels, and calcium channel activators.

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Section: Fertilitymentioning

confidence: 99%

“…146,147 T-type channels are found in human sperm, and both the a 1 G and a 1 H transcripts have been reported. [147][148][149] The acrosome response is blocked by mibefradil at micromolar concentrations. It is of interest that gossypol, a male antifertility compound that has been used in China, is an inhibitor of murine T-type Ca 21 channels.…”

Section: Fertilitymentioning

confidence: 99%

Drug Targets in the Voltage-Gated Calcium Channel Family: Why Some Are and Some Are Not

Triggle

2003

ASSAY and Drug Development Technologies

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“…Mannose-BSA has been shown to increase Ca 2þ i in human sperm, which accounts for its ability to induce the AR (Blackmore & Eisoldt 1999). Previous observations indicated that Ca V channels may be involved in the actions of mannose-BSA (Blackmore & Eisoldt 1999, Son et al 2000), although a potential mannose-BSA-induced internal Ca 2þ rise by a different activation pathway cannot be ruled out. Lastly, the linearity of movement was apparently increased in Ca V 2.3 null sperm (Sakata et al 2002), suggesting that these channels may be functional in sperm and may play roles in Ca 2þ i signals and the control of flagellar motility.…”

Section: Camentioning

confidence: 96%

Molecular physiology and pathology of Ca2+-conducting channels in the plasma membrane of mammalian sperm

Felix¹

2005

Reproduction

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Current evidence indicates that mechanisms controlling the intracellular Ca 21 concentration play pivotal roles in determining sperm fertilizing ability. Multiple Ca 21 -permeable channels have been identified and characterized in the plasma membrane and in the acrosome membrane of mammalian sperm. This review summarizes the recent findings and assesses the evidence suggesting that these channels play roles in controlling a host of sperm functions ranging from motility to the acrosome reaction, and describes recent advances in the identification of the underlying gene defects of inherited sperm Ca

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“…Abnormal Ca 2þ currents through conformationally defective dihydropyridinesensitive Ca 2þ channels (L-type VDCC) have been observed in infertile, but not fertile, men [20], suggesting pivotal role of L-type Ca 2þ channels in the development of male fertility in humans. Functional T-type Ca 2þ channel, which belongs to LVA Ca 2þ channel, has been identified in the meiotic and post-meiotic germ cells including spermatozoa [2,23,[26][27][28][29][30]. In human, treatment of Ca 2þ channel blocker (CCB) to relieve hypertension causes reversible male infertility [13,15].…”

Section: Introductionmentioning

confidence: 99%

Effects of Calcium Channel Blockers on the Spermatogenesis and Gene Expression in Peripubertal Mouse Testis

Lee

Kim

et al. 2006

Archives of Andrology

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Treatment of Ca(2+) channel blockers (CCB) to relieve hypertension causes reversible male infertility, suggesting deregulation of Ca(2+) homeostasis in testis is closely related with male infertility. To investigate the possible toxicity of therapeutic application of CCB in childhood, the effect of nifedipine and ethosuximide, an L-type and T-type CCB, respectively, on the spermatogenesis and testicular gene expression was examined. Following the intraperitoneal injection of either drug for 7 days to 18 days on old mice, the paired testes weights were significantly lower in mice treated with nifedipine (> or = 10 mg/kg/day) or ethosuximide (100 mg/kg/day) than vehicle controls. In mice given high drug dosing (100 mg/kg), seminiferous tubules showed immaturity with spermatogenic arrest at elongating spermatid stage and poorly developed lumen. Unexpectedly, the expression of activator isoform of transcription factor cAMP-responsive element modulator (CREM) mRNA increased together with transition protein 2 and protamine 2 mRNA in drug-treated mice testes, suggesting that CCB may deregulate expression of activator isoform of CREM in male germ cells and that spermatogenic defect following CCB treatment may attribute to ectopic expression of CREM-dependent gene battery in testis. Therapeutic application of CCB in childhood should be cautious because of their potential to cause spermatogenic defect and altered gene expression in testis.

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Acrosome Reaction of Human Spermatozoa Is Mediated Mainly by α1H T-Type Calcium Channels

Cited by 9 publications

References 0 publications

Drug Targets in the Voltage-Gated Calcium Channel Family: Why Some Are and Some Are Not

Drug Targets in the Voltage-Gated Calcium Channel Family: Why Some Are and Some Are Not

Molecular physiology and pathology of Ca2+-conducting channels in the plasma membrane of mammalian sperm

Effects of Calcium Channel Blockers on the Spermatogenesis and Gene Expression in Peripubertal Mouse Testis

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