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Role of CK2 and calcineurin in increased NMDA receptor activity of PVN presympathetic neurons in hypertension
Author(s) -
Ye Zengyou,
Li DePei,
Pan HuiLin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1019.13
Subject(s) - nmda receptor , ampa receptor , endocrinology , medicine , calcineurin , chemistry , glutamate receptor , dephosphorylation , receptor , neuroscience , phosphatase , phosphorylation , biology , biochemistry , transplantation
Increased glutamatergic input to presympathetic neurons in the paraventricular nucleus (PVN) plays a critical role in increased sympathetic outflow in hypertension. However, the molecular mechanism underlying increased NMDA receptor activity in the PVN in hypertension is not known. Here we determined the role of protein kinase CK2 and protein phosphatase calcineurin in regulating NMDA receptor activity in spinally projecting PVN neurons in brain slices from spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY). The NMDA current (0.68 ± 0.05 vs. 0.32 ± 0.06 pA/pF, P < 0.05) and the ratio (0.72 ± 0.07 vs. 0.35 ± 0.02, P < 0.05) of NMDA/AMPA currents of retrogradely labeled PVN neurons were significantly larger in SHR than in WKY. Inhibition of CK2 with DRB or TBB normalized the increase in NMDA currents and had no effect on AMPA currents in SHR. Inhibition of calcineurin with FK506 significantly increased NMDA currents in WKY but not in SHR. Furthermore, in the presence of FK506, DRB had little effect on NMDA currents in SHR and WKY. Our study provides important new information that the phosphorylation and dephosphorylation process tonically regulates NMDA receptor function. The imbalance between CK2 and calcineurin activity in the PVN likely contributes to augmented NMDA receptor activity in presympathetic neurons and increased sympathetic outflow in hypertension.