The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca 2+

Volodymyr Rybalchenko, Michael A. Grillo, Matthew J. Gastinger, Nataliya Rybalchenko, Andrew J. Payne, Peter Koulen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Ca2+ release from intracellular stores mediated by endoplasmic reticulum membrane ryanodine receptors (RyR) plays a key role in activating and synchronizing downstream Ca2+-dependent mechanisms, in different cells varying from apoptosis to nuclear transcription and development of defensive responses. Recently discovered, atypical "nongenomic" effects mediated by estrogen receptors (ER) include rapid Ca2+ release upon estrogen exposure in conditions implicitly suggesting involvement of RyRs. In the present study, we report various levels of colocalization between RyR type 2 (RyR2) and ER type β (ERβ) in the neuronal cell line HT-22, indicating a possible functional interaction. Electrophysiological analyses revealed a significant increase in single-channel ionic currents generated by mouse brain RyRs after application of the soluble monomer of the long form ERβ (ERβ 1). The effect was due to a strong increase in open probability of RyR higher open channel sublevels at cytosolic [Ca2+] concentrations of 100nM, suggesting a synergistic action of ERβ1 and Ca2+ in RyR activation, and a potential contribution to Ca 2+-induced Ca2+ release rather than to basal intracellular Ca2 concentration level at rest. This RyR/ERβ interaction has potential effects on cellular physiology, including roles of shorter ERβ isoforms and modulation of the RyR/ERβ complexes by exogenous estrogens.

Original languageEnglish (US)
Pages (from-to)326-341
Number of pages16
JournalJournal of Receptors and Signal Transduction
Volume29
Issue number6
DOIs
StatePublished - Dec 1 2009

Keywords

  • -estradiol
  • 17β
  • Electrophysiology
  • Endocrinology
  • Intracellular calcium stores
  • Nervous system
  • Neuron

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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