A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities

Yanyan Geng, Juan J. Ferreira, Victor Dzikunu, Alice Butler, Pascale Lybaert, Peng Yuan, Karl L. Magleby, Lawrence Salkoff, Celia M. Santi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K+) channels and resultant K+ efflux. Sperm-specific SLO3 K+ channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pHi. However, in human sperm, the major K+ conductance is both Ca2+-and pHi-sensitive. It has been debated whether Ca2+-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembranegated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca2+, the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.

Original languageEnglish (US)
Pages (from-to)8978-8987
Number of pages10
JournalJournal of Biological Chemistry
Volume292
Issue number21
DOIs
StatePublished - May 26 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Geng, Y., Ferreira, J. J., Dzikunu, V., Butler, A., Lybaert, P., Yuan, P., Magleby, K. L., Salkoff, L., & Santi, C. M. (2017). A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities. Journal of Biological Chemistry, 292(21), 8978-8987. https://doi.org/10.1074/jbc.M117.776013