Defective Function of Membrane Potential (Ψ) on Sperm of Infertile Men

Calzada, L; Tellez, J.

doi:10.3109/01485019708987892

Cited by 20 publications

(18 citation statements)

References 12 publications

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“…Several K C channels exist in spermatozoa (Darszon et al 1999, and future studies are necessary to determine if there is a specific functional relationship between a4 and one of the particular K C channel expressed in sperm. An adequate membrane potential is essential for sperm motility, and cell membrane depolarization has been shown to be associated to infertility in asthenozoospermic patients (Calzada & Tellez 1997). Our results therefore suggest that one of the mechanisms by which the a4 isoform influences sperm motility is through its key role in maintaining the uneven transmembrane distribution of Na C and K C , and the electrical potential of the sperm plasma membrane.…”

Section: Discussionmentioning

confidence: 53%

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

Jiménez

Sánchez²,

Wertheimer³

et al. 2010

Reproduction

104

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While the function of the ubiquitous Na,K-ATPase a1 subunit has been well documented, the role of the sperm-specific a4 isoform of this ion transporter is less known. We have explored the importance of a4 in rat sperm physiology by taking advantage of the high sensitivity of this isoform for the inhibitor ouabain. Using concentrations that selectively block a4 activity, we found ouabain to reduce not only sperm total motility, but also multiple parameters of sperm movement, including progressive motility, straight line, curvilinear, and average path velocities, lateral head displacement, beat cross frequency, and linearity. According to a direct role of a4 in Na C transport, ouabain inhibition of a4 increased [Na C ] i in the male gametes. In addition, interference of a4 activity with ouabain produced cell membrane depolarization, diminished pH, and increased [Ca 2C ] i in spermatozoa. Inhibition of a4 was sufficient to cause all these effects and additional blockage of a1, the other Na,K-ATPase a isoform expressed in sperm, and higher doses of ouabain did not result in further changes in the cell parameters studied. These results show that a4 is the Na,K-ATPase isoform primarily involved in controlling the transmembrane Na C gradient in sperm, and that a4 activity is necessary for maintaining membrane potential, [Ca ] i , and acid-base balance suggests that their regulation is the mechanism by which a4 maintains motility of the male gametes.

show abstract

Section: Discussionmentioning

confidence: 53%

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

Jiménez

Sánchez²,

Wertheimer³

et al. 2010

Reproduction

104

View full text Add to dashboard Cite

show abstract

“…In addition, appropriate values of plasma membrane potential are required for sperm motility and during sperm capacitation (24). Moreover, cell membrane depolarization is associated with infertility in patients with asthenozoospermia (25). Our results highlight the importance of ion balance and membrane excitability as the mechanisms by which the α4 isoform supports sperm motility.…”

Section: Discussionmentioning

confidence: 73%

Na,K-ATPase α4 isoform is essential for sperm fertility

Jiménez

McDermott

Sánchez

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

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Regulation of ion balance in spermatozoa has been shown to be essential for sperm motility and fertility. Control of intracellular ion levels requires the function of distinct ion-transport mechanisms at the cell plasma membrane. Active Na + and K + exchange in sperm is under the control of the Na,K-ATPase. Two molecular variants of the catalytic subunit of the Na,K-ATPase, α1 and α4, coexist in sperm. These isoforms exhibit different biochemical properties; however, their function in sperm fertility is unknown. In this work, we show that Na,K-ATPase α4 is essential for sperm fertility. Knockout male mice lacking α4 are completely sterile and spermatozoa from these mice are unable of fertilizing eggs in vitro. Furthermore, α4 deletion results in severe reduction in sperm motility and hyperactivation typical of sperm capacitation. In addition, absence of α4 causes a characteristic bend in the sperm flagellum, indicative of abnormal sperm ion regulation. Accordingly, α4-null sperm present increased intracellular Na + and cell plasma membrane depolarization. These results are unique in demonstrating the absolute requirement of α4 for sperm fertility. Moreover, the inability of α1 to compensate for α4 suggests that α4 is the Na,K-ATPase-α isoform directly involved in sperm fertility. Our findings show α4 as an attractive target for male contraception and open the possibility for the potential use of this Na,K-ATPase isoform as a biomarker for male fertility.

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“…The plasma membrane potential of a spermatozoon undergoes many changes throughout maturation that are critical for its ability to fertilize the ovum; therefore, precise regulation of the plasma membrane potential is necessary for normal sperm function (41). Previous studies using bull sperm have shown that ouabain decreases the progressive motility and flagellar wave of sperm and that the membrane potential of these sperm is dramatically more positive, providing a connection between the regulation of membrane potential and sperm motility (42).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a recent study of immotile sperm collected from asthenozoospermic, infertile humans demonstrated that they exhibit both decreased motility and dramatically less negative plasma membrane potentials compared with sperm from healthy, normal, fertile men (41). Again, the contribution of individual Na,K-ATPase ␣ isoforms was not considered, but future studies of these infertile patients may reveal the absence of, or dysfunctional, Na,K-ATPase carrying the ␣4 isoform.…”

Section: Discussionmentioning

confidence: 99%

Sperm Motility Is Dependent on a Unique Isoform of the Na,K-ATPase

Woo

James

Lingrel³

2000

Journal of Biological Chemistry

146

164

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The Na,K-ATPase, a member of the P-type ATPases, is composed of two subunits, ␣ and ␤, and is responsible for translocating Na ؉ out of the cell and K ؉ into the cell using the energy of hydrolysis of one molecule of ATP. The electrochemical gradient it generates is necessary for many cellular functions, including establishment of the plasma membrane potential and transport of sugars and ions in and out of the cell. Families of isoforms for both the ␣ and ␤ subunits have been identified, and specific functional roles for individual isoforms are just beginning to emerge. The ␣4 isoform is the most recently identified Na,K-ATPase ␣ isoform, and its expression has been found only in testis. Here we show that expression of the ␣4 isoform in testis is localized to spermatozoa and that inhibition of this isoform alone eliminates sperm motility. These data describe for the first time a biological function for the ␣4 isoform of the Na,KATPase, revealing a critical role for this isoform in sperm motility.

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Defective Function of Membrane Potential (Ψ) on Sperm of Infertile Men

Cited by 20 publications

References 12 publications

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

Na,K-ATPase α4 isoform is essential for sperm fertility

Sperm Motility Is Dependent on a Unique Isoform of the Na,K-ATPase

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