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

作者：Geng Yanyan; Ferreira Juan J; Dzikunu Victor; Butler Alice; Lybaert Pascale; Yuan Peng; Magleby Karl L; Salkoff Lawrence; Santi Celia M^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292(21): 8978-8987.

DOI：10.1074/jbc.M117.776013

• fertilization
• patch clamp
• potassium channel
• reproduction
• sperm
• spermatozoa
• calcium sensitivity
• genetic variant
• human SLO3
• pH sensitivity

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 pH(i). However, in human sperm, the major K+ conductance is both Ca2+- and pH(i)-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 intramembrane-gated 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.

• 出版日期2017-5-26