Protein Kinase CK2 Increases Glutamatergic Input in the Hypothalamus and Sympathetic Vasomotor Tone in Hypertension
Open Access
- 1 June 2011
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (22), 8271-8279
- https://doi.org/10.1523/jneurosci.1147-11.2011
Abstract
Increased glutamatergic input in the paraventricular nucleus (PVN) is important for high sympathetic outflow in hypertension, but the associated molecular mechanisms remain unclear. Here, we determined the role of protein kinase CK2 (formerly casein kinase II) in increasedN-methyl-d-aspartate receptor (NMDAR) activity in spinally projecting PVN neurons and sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The selective CK2 inhibitors 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) or 4,5,6,7-tetrabromobenzotriazole (TBB) significantly decreased the frequency of miniature EPSCs (mEPSCs) of labeled PVN neurons in SHRs but not in Wistar-Kyoto (WKY) normotensive rats. Also, DRB abolished the inhibitory effect of the NMDAR antagonist AP5 on the frequency of mEPSCs in SHRs. Treatment with DRB or TBB significantly reduced the amplitude of evoked NMDA-EPSCs but not AMPA-EPSCs in SHRs. Furthermore, DRB significantly decreased the firing activity of PVN neurons in SHRs but not in WKY rats. The membrane protein level of CK2α in the PVN, but not brainstem and prefrontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased CK2α level and the effects of DRB on mEPSCs and NMDA-EPSCs. In addition, intracerebroventricular injection of DRB not only significantly reduced blood pressure and lumbar sympathetic nerve discharges but also eliminated the inhibitory effect of AP5 microinjected into the PVN on sympathetic nerve activity in SHRs. Our findings suggest that augmented CK2 activity critically contributes to increased presynaptic and postsynaptic NMDAR activity in the PVN and elevated sympathetic vasomotor tone in essential hypertension.This publication has 52 references indexed in Scilit:
- Opioid-Induced Long-Term Potentiation in the Spinal Cord Is a Presynaptic EventJournal of Neuroscience, 2010
- CK2 Is the Regulator of SIRT1 Substrate-Binding Affinity, Deacetylase Activity and Cellular Response to DNA-DamagePLOS ONE, 2009
- CK2β Is Expressed in Endometrial Carcinoma and Has a Role in Apoptosis Resistance and Cell ProliferationThe American Journal of Pathology, 2009
- Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampusJournal Of Physiology-London, 2008
- Regulation of the Epithelial Na+ Channel by the Protein Kinase CK2Online Journal of Public Health Informatics, 2008
- Pre‐ and postsynaptic plasticity underlying augmented glutamatergic inputs to hypothalamic presympathetic neurons in spontaneously hypertensive ratsJournal Of Physiology-London, 2008
- The Alpha Catalytic Subunit of Protein Kinase CK2 Is Required for Mouse Embryonic DevelopmentMolecular and Cellular Biology, 2008
- Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in HypertensionHypertension, 2007
- Protein kinase CK2 in postsynaptic densities: phosphorylation of PSD-95/SAP90 and NMDA receptor regulationBiochemical and Biophysical Research Communications, 2004
- VR1 Receptor Activation Induces Glutamate Release and Postsynaptic Firing in the Paraventricular NucleusJournal of Neurophysiology, 2004