Celia M. Santi, M.D., Ph.D.

Associate Professor
Obstetrics and Gynecology

Molecular Cell Biology Program

  • 314 747-3306

  • 314-273-0120

  • santic@wustl.edu

  • male fertility, ion channels, sperm physiology,

  • Aspects of sexual reproduction that involve membrane excitability and control of membrane voltage in spermatozoa, which are essential for the sperm to fertilize the egg

Research Abstract:

The interactions of the gametes involved in sexual reproduction represent a microcosm of molecular cell biology and physiology. My lab research focuses on those aspects of sexual reproduction that involve membrane excitability and control of membrane voltage in spermatozoa, which are essential for the sperm to fertilize the egg. During development sperm mature in the epididymis where they remain quiescent. However, upon release from the epididymis they must undergo marked changes to increase their motility and capacity to fertilize the egg. These changes are labeled sperm capacitation and involve the acquisition of hyperactivated motility, and the ability to undergo the acrosome reaction, which entails a voltage and calcium-dependent exocytotic event. Ion channels in
the sperm plasma membrane are essential molecules in the signaling processes that control sperm capacitation and have been the focus of my lab’s attention.

My lab previously established that the pH-dependent SLO3 potassium channel is essential for male fertility. The knock-out of this sperm-specific potassium channel confers total male-specific infertility with major defects in sperm motility and the acrosome reaction. We are studying the SLO3 channel in the following areas:

1) We are using the SLO3 KO mouse to dissect the pathways activated by or linked to membrane voltage control.

2) We are carrying on experiments in bovine and human sperm to determine if the participation of SLO3 channels in sperm membrane voltage control is conserved in mammals.

3) In order to understand how SLO3 channels work and how they are modulated, we are using comparative genomics to get fundamental insights about the basic function, development, and regulation of potassium channels, and their role in behavior.

Selected Publications:

K+ and Cl- channels and transporters in sperm function.
Santi CM, Orta G, Salkoff L, Visconti PE, Darszon A, Treviño CL.
Current topics in developmental biology. 2013; 102:385-421. NIHMSID: NIHMS467352
PubMed [journal]PMID: 23287041 PMCID: PMC3670610

Ion permeabilities in mouse sperm reveal an external trigger for SLO3-dependent hyperpolarization.
Chávez JC, de la Vega-Beltrán JL, Escoffier J, Visconti PE, Treviño CL, Darszon A, Salkoff L, Santi CM.
PloS one. 2013; 8(4):e60578.
PubMed [journal]PMID: 23577126 PMCID: PMC3618424

Membrane hyperpolarization during human sperm capacitation.
López-González I, Torres-Rodríguez P, Sánchez-Carranza O, Solís-López A, Santi CM, Darszon A, Treviño CL.
Molecular human reproduction. 2014; 20(7):619-29.
PubMed [journal]PMID: 24737063 PMCID: PMC4072184

SLO3 K+ channels control calcium entry through CATSPER channels in sperm.
Chávez JC, Ferreira JJ, Butler A, De La Vega Beltrán JL, Treviño CL, Darszon A, Salkoff L, Santi CM.
The Journal of biological chemistry. 2014; 289(46):32266-75.
PubMed [journal]PMID: 25271166 PMCID: PMC4231700

Flow cytometry analysis reveals that only a subpopulation of mouse sperm undergoes hyperpolarization during capacitation.
Escoffier J, Navarrete F, Haddad D, Santi CM, Darszon A, Visconti PE.
Biology of reproduction. 2015; 92(5):121.
PubMed [journal]PMID: 25855261 PMCID: PMC4645980

Src Kinase Is the Connecting Player between Protein Kinase A (PKA) Activation and Hyperpolarization through SLO3 Potassium Channel Regulation in Mouse Sperm.
Stival C, La Spina FA, Baró Graf C, Arcelay E, Arranz SE, Ferreira JJ, Le Grand S, Dzikunu VA, Santi CM, Visconti PE, Buffone MG, Krapf D.
The Journal of biological chemistry. 2015; 290(30):18855-64.
PubMed [journal]PMID: 26060254 PMCID: PMC4513139

SLO2 Channels Are Inhibited by All Divalent Cations That Activate SLO1 K+ Channels.
Budelli G, Sun Q, Ferreira J, Butler A, Santi CM, Salkoff L.
The Journal of biological chemistry. 2016; 291(14):7347-56.
PubMed [journal]PMID: 26823461 PMCID: PMC4817167

Geng Y, Ferreira JJ, Dzikunu V, Butler A, Lybaert P, Yuan P, Magleby KL, Salkoff L,
Santi CM. A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities. J. Biol. Chem. (2017) May 26;292(21):8978-8987.

Last Updated: 7/25/2018 8:19:20 AM

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