The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+.
Ca(2+) release from intracellular stores mediated by endoplasmic reticulum membrane ryanodine receptors (RyR) plays a key role in activating and synchronizing downstream Ca(2+)-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 Ca(2+) 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 beta (ER beta) 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 ER beta (ER beta 1). The effect was due to a strong increase in open probability of RyR higher open channel sublevels at cytosolic [Ca(2+)] concentrations of 100 nM, suggesting a synergistic action of ER beta 1 and Ca(2+) in RyR activation, and a potential contribution to Ca(2+)-induced Ca(2+) release rather than to basal intracellular Ca(2+) concentration level at rest. This RyR/ER beta interaction has potential effects on cellular physiology, including roles of shorter ER beta isoforms and modulation of the RyR/ER beta complexes by exogenous estrogens.
Rybalchenko
Volodymyr
V
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Grillo
Michael A
MA
Gastinger
Matthew J
MJ
Rybalchenko
Nataliya
N
Payne
Andrew J
AJ
Koulen
Peter
P
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*
D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium