TY - JOUR
T1 - The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca 2+
AU - Rybalchenko, Volodymyr
AU - Grillo, Michael A.
AU - Gastinger, Matthew J.
AU - Rybalchenko, Nataliya
AU - Payne, Andrew J.
AU - Koulen, Peter
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - -estradiol
KW - 17β
KW - Electrophysiology
KW - Endocrinology
KW - Intracellular calcium stores
KW - Nervous system
KW - Neuron
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U2 - 10.3109/10799890903295168
DO - 10.3109/10799890903295168
M3 - Article
C2 - 19899956
AN - SCOPUS:71149102640
SN - 1079-9893
VL - 29
SP - 326
EP - 341
JO - Journal of Receptors and Signal Transduction
JF - Journal of Receptors and Signal Transduction
IS - 6
ER -