mRNA expression of ion channels in GnRH neurons: subtype-specific regulation by 17β-estradiol

Mol Cell Endocrinol. 2013 Mar 10;367(1-2):85-97. doi: 10.1016/j.mce.2012.12.021. Epub 2013 Jan 7.

Abstract

Burst firing of neurons optimizes neurotransmitter release. GnRH neurons exhibit burst firing activity and T-type calcium channels, which are vital for burst firing activity, are regulated by 17β-estradiol (E2) in GnRH neurons. To further elucidate ion channel expression and E2 regulation during positive and negative feedback on GnRH neurosecretion, we used single cell RT-PCR and real-time qPCR to quantify channel mRNA expression in GnRH neurons. GFP-GnRH neurons expressed numerous ion channels important for burst firing activity. E2-treatment sufficient to induce an LH surge increased mRNA expression of HCN1 channels, which underlie the pacemaker current, the calcium-permeable Ca(V)1.3, Ca(V)2.2, Ca(V)2.3 channels, and TRPC4 channels, which mediate the kisspeptin excitatory response. E2 also decreased mRNA expression of SK3 channels underlying the medium AHP current. Therefore, E2 exerts fundamental changes in ion channel expression in GnRH neurons, to prime them to respond to incoming stimuli with increased excitability at the time of the surge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estradiol / pharmacology*
  • Feedback, Physiological / drug effects
  • Female
  • Gene Expression Regulation / drug effects*
  • Gonadotropin-Releasing Hormone / metabolism*
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Luteinizing Hormone / blood
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism*
  • Ovariectomy
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Kisspeptin-1
  • Regression Analysis

Substances

  • Ion Channels
  • KISS1R protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Luteinizing Hormone