Veratridine-sensitive Na + channels regulate human sperm fertilization capacity

Life Sci. 2018 Mar 1;196:48-55. doi: 10.1016/j.lfs.2018.01.004. Epub 2018 Jan 4.

Abstract

Aims: The sperm plasma membrane contains specific ion channels and transporters that initiate changes in Ca2+, Na+, K+ and H+ ions in the sperm cytoplasm. Ion channels are key regulators of the sperm membrane potential, cytoplasmic Ca2+ and intracellular pH (pHi), which leads to regulate motility, capacitation, acrosome reaction and other physiological processes crucial for successful fertilization. Expression of epithelial sodium channels (ENaC) and voltage-gated sodium channels (Nav) in human spermatozoa has been reported, but the role of Na+ fluxes sodium channels in the regulation of sperm cell function remains poorly understood. In this context, we aimed to analyze the physiological role of Nav channels in human sperm.

Main methods: Motility and hyperactivation analysis was conducted by CASA analysis. Flow cytometry and spectrophotometry approaches were carried out to measure Capacitation, Acrosome reaction, immunohistochemistry for Tyr-residues phosporylation, [Ca2+]i levels and membrane potential.

Key findings: Functional studies showed that veratridine, a voltage-gated sodium channel activator, increased sperm progressive motility without producing hyperactivation while the Nav antagonist lidocaine did induce hyperactivated motility. Veratridine increased protein tyrosine phosphorylation, an event occurring during capacitation, and its effects were inhibited in the presence of lidocaine and tetrodotoxin. Veratridine had no effect on the acrosome reaction by itself, but was able to block the progesterone-induced acrosome reaction. Moreover, veratridine caused a membrane depolarization and modified the effect of progesterone on [Ca2+]i and sperm membrane potential.

Significance: Our results suggest that veratridine-sensitive Nav channels are involved on human sperm fertility acquisition regulating motility, capacitation and the progesterone-induced acrosome reaction in human sperm.

Keywords: Human sperm fertility; Membrane potential; Na(v) channels; Tyrosine phosphorylation; Veratridine.

MeSH terms

  • Acrosome Reaction / drug effects
  • Adolescent
  • Adult
  • Female
  • Fertilization / drug effects*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Lidocaine / pharmacology
  • Male
  • Membrane Potentials / drug effects
  • Progesterone / antagonists & inhibitors
  • Progesterone / pharmacology
  • Receptors, Androgen / drug effects
  • Semen / drug effects
  • Sodium / metabolism
  • Sodium Channel Agonists / pharmacology*
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / drug effects*
  • Sperm Capacitation / drug effects
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects*
  • Veratridine / pharmacology*
  • Young Adult

Substances

  • Receptors, Androgen
  • Sodium Channel Agonists
  • Sodium Channel Blockers
  • Sodium Channels
  • Progesterone
  • Veratridine
  • Lidocaine
  • Sodium