Small-conductance, calcium-activated potassium channel 3 (SK3) is a modulator of endometrial remodeling during endometrial growth

J Clin Endocrinol Metab. 2014 Oct;99(10):3800-10. doi: 10.1210/jc.2013-3389. Epub 2014 Jun 30.


Background: Small-conductance, Ca(2+)-activated K(+) channel 3 (SK3) has been shown to be expressed in porcine endometrium. However, the roles of SK3 in human endometrium during the menstrual cycle and early pregnancy are unknown.

Objective: The objective of the study was to investigate the expression and function of SK3 in human endometrium and the mechanism involved.

Methods: We determined the expression of SK3 in human endometrium by RT-PCR, Western blotting, and immunofluorescence. Using electrophysiological and fluorescent imaging techniques, we investigated the effects of SK3 on the membrane potential and the concentrations of cytosolic calcium, respectively. The effects of SK3 on endometrial thickness and pregnancy outcome were also investigated. Knockdown of endometrial SK3 was used to examine the effects of SK3 on cell migration, cytoskeleton formation, and calcium concentration in the cytosol.

Results: SK3 channels are present in human endometrium. In vivo experimental and clinical data demonstrated that the reduced expression of SK3 was associated with a thin endometrium and unsuccessful pregnancy outcomes. Knockdown of human endometrial SK3 attenuated the rise in cytosolic calcium and membrane hyperpolarization induced by thapsigargin, a Ca(2+)-ATPase inhibitor, cell migration, and F-actin assembly. Knockdown of endometrial SK3 in mice also resulted in a thin endometrium and unsuccessful pregnancy outcome.

Conclusions: These observations demonstrate that SK3 channels are expressed in human endometrial cells. Reduced SK3 expression attenuates endometrial cell migration and is associated with unsuccessful pregnancy outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Movement / physiology
  • Endometrium / cytology*
  • Endometrium / growth & development*
  • Endometrium / metabolism
  • Female
  • Fertilization in Vitro
  • Gene Knockdown Techniques
  • Humans
  • Membrane Potentials / physiology
  • Menstrual Cycle / genetics
  • Menstrual Cycle / metabolism*
  • Mice, Inbred ICR
  • Pregnancy
  • Pregnancy Outcome
  • Primary Cell Culture
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Sperm Injections, Intracytoplasmic


  • KCNN1 protein, human
  • KCNN2 protein, human
  • KCNN3 protein, human
  • Kcnn1 protein, mouse
  • Kcnn2 protein, mouse
  • Kcnn3 protein, mouse
  • Small-Conductance Calcium-Activated Potassium Channels
  • Calcium