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ROLES OF THE Na,K-ATPase ALPHA AND Na/H EXCHANGER (NHE) ISOFORMS, pH AND PROTEIN KINASE A (PKA) IN SPERM PHYSIOLOGY: REGULATION OF SPERM MOTILITY AND ACROSOMAL EXOCYTOSIS

Sengupta, Arunima
http://rave.ohiolink.edu/etdc/view?acc_num=miami1184613444

Abstract Details

2007, Doctor of Philosophy, Miami University, Zoology.
Acquisition and maintenance of motility and acrosomal exocytosis are important components of sperm physiology in that they play critical roles in ensuring fertility. The roles that membrane transporters play in regulating sperm motility and acrosomal exocytosis are not well understood. However, recent evidence suggests that the coordinated activity of the Na,K-ATPase alpha4 isoform and a NHE is important in maintaining an optimal intracellular pH critical for sperm motility. In addition, knockout of the sperm-specific NHE, NHE10, results in immotile mouse sperm confirming a link between NHE activity and sperm motility. NHE10 knockout sperm motility can be restored either by increasing intracellular pH or by stimulating protein kinase A (PKA) suggesting that PKA either bypasses the inhibitory effect of pH on motility or that PKA directly affects a pH-dependent motility regulating pathway in sperm. In this study, the inter-relationship between the Na,K-ATPase alpha4 isoform, the NHE, intracellular pH, and PKA in sperm motility and in acrosomal exocytosis were examined. Data presented here demonstrate that stimulation of PKA can reinitiate motility of cytoplasmically acidified sperm only in the presence of an active NHE. Furthermore, it was found that PKA is upstream of a Na,K-ATPase alpha4-dependent, NHE-induced intracellular pH change in a single motility-restoring pathway. In addition, our results show that PKA influences Na,K-ATPase activity at least partially by inhibiting ouabain’s ability to bind to the alpha4 isoform. In an effort to determine which NHEs are involved in this PKA-mediated motility restoration, a novel role for NHE as a receptor which can transduce a signaling cascade via sAC/cAMP/PKA-dependent mechanism was uncovered. Finally, our data demonstrate that inhibition of both the Na,K-ATPase and NHE result in significant increases in the percentage of sperm undergoing acrosomal exocytosis, highlighting important roles for these transporters in the regulation of sperm capacitation in addition to their regulatory roles in maintaining sperm motility.
Paul James (Advisor)
124 p.
Biology, Animal Physiology

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Citations

  • Sengupta, A. (2007). ROLES OF THE Na,K-ATPase ALPHA AND Na/H EXCHANGER (NHE) ISOFORMS, pH AND PROTEIN KINASE A (PKA) IN SPERM PHYSIOLOGY: REGULATION OF SPERM MOTILITY AND ACROSOMAL EXOCYTOSIS [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1184613444

    APA Style (7th edition)

  • Sengupta, Arunima. ROLES OF THE Na,K-ATPase ALPHA AND Na/H EXCHANGER (NHE) ISOFORMS, pH AND PROTEIN KINASE A (PKA) IN SPERM PHYSIOLOGY: REGULATION OF SPERM MOTILITY AND ACROSOMAL EXOCYTOSIS. 2007. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1184613444.

    MLA Style (8th edition)

  • Sengupta, Arunima. "ROLES OF THE Na,K-ATPase ALPHA AND Na/H EXCHANGER (NHE) ISOFORMS, pH AND PROTEIN KINASE A (PKA) IN SPERM PHYSIOLOGY: REGULATION OF SPERM MOTILITY AND ACROSOMAL EXOCYTOSIS." Doctoral dissertation, Miami University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=miami1184613444

    Chicago Manual of Style (17th edition)

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© 2007, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.