α2δ‐1 couples to NMDA receptors in the hypothalamus to sustain sympathetic vasomotor activity in hypertension

α2δ‐1 is upregulated, promoting the interaction with NMDA receptors (NMDARs), in the hypothalamus in a rat model of hypertension. The prevalence of α2δ‐1–bound NMDARs at synaptic sites in the hypothalamus is increased in hypertensive animals. α2δ‐1 is essential for the increased presynaptic and postsynaptic NMDAR activity of hypothalamic neurons in hypertension. α2δ‐1–bound NMDARs in the hypothalamus are critically involved in augmented sympathetic outflow in hypertensive animals.

[1]  H. Pan,et al.  Endogenous AT1 receptor–protein kinase C activity in the hypothalamus augments glutamatergic input and sympathetic outflow in hypertension , 2019, The Journal of physiology.

[2]  H. Pan,et al.  &agr;2&dgr;-1–Bound N-Methyl-D-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents , 2019, Anesthesiology.

[3]  H. Pan,et al.  Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain , 2019, Cellular and Molecular Life Sciences.

[4]  David M. Reboussin,et al.  Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines , 2018, Hypertension.

[5]  David M. Maclean,et al.  The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions , 2022, Cell reports.

[6]  G. Feng,et al.  Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis. , 2017, Cell reports.

[7]  De-Pei Li,et al.  CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension , 2017, The Journal of Neuroscience.

[8]  De-Pei Li,et al.  Src Kinases Regulate Glutamatergic Input to Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension , 2017, Hypertension.

[9]  J. Lund,et al.  Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis , 2016, Canadian Journal of Anesthesia/Journal canadien d'anesthésie.

[10]  Sang-beom Jeon,et al.  Paroxysmal Sympathetic Hyperactivity After Acute Brain Injury , 2013, Current Neurology and Neuroscience Reports.

[11]  G. Dibona.  Sympathetic nervous system and hypertension. , 2013, Hypertension.

[12]  H. Byun,et al.  NKCC1 Upregulation Disrupts Chloride Homeostasis in the Hypothalamus and Increases Neuronal Activity–Sympathetic Drive in Hypertension , 2012, The Journal of Neuroscience.

[13]  H. Pan 潘,et al.  Casein Kinase 2-mediated Synaptic GluN2A Up-regulation Increases N-Methyl-d-aspartate Receptor Activity and Excitability of Hypothalamic Neurons in Hypertension* , 2012, The Journal of Biological Chemistry.

[14]  A. Panchenko,et al.  Phosphorylation in protein-protein binding: effect on stability and function. , 2011, Structure.

[15]  D. Hoffman,et al.  Pregabalin is a potent and selective ligand for α(2)δ-1 and α(2)δ-2 calcium channel subunits. , 2011, European journal of pharmacology.

[16]  Z. Ye,et al.  Protein Kinase CK2 Increases Glutamatergic Input in the Hypothalamus and Sympathetic Vasomotor Tone in Hypertension , 2011, The Journal of Neuroscience.

[17]  B. Fakler,et al.  Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain , 2010, Proceedings of the National Academy of Sciences.

[18]  De-Pei Li,et al.  Aminopyridines Potentiate Synaptic and Neuromuscular Transmission by Targeting the Voltage-activated Calcium Channel β Subunit*♦ , 2009, The Journal of Biological Chemistry.

[19]  Sheryl E. Koch,et al.  Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. , 2009, American Journal of Physiology. Heart and Circulatory Physiology.

[20]  C. Taylor,et al.  Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (α2-δ) type 1 protein , 2008, Neuroscience.

[21]  Qing Yang,et al.  Pre‐ and postsynaptic plasticity underlying augmented glutamatergic inputs to hypothalamic presympathetic neurons in spontaneously hypertensive rats , 2008, The Journal of physiology.

[22]  De-Pei Li,et al.  Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension , 2007, Hypertension.

[23]  A. Paraskeva,et al.  Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal intubation. , 2006, British journal of anaesthesia.

[24]  De-Pei Li,et al.  Plasticity of GABAergic control of hypothalamic presympathetic neurons in hypertension. , 2006, American journal of physiology. Heart and circulatory physiology.

[25]  Mark E. Williams,et al.  Differential distribution of voltage‐gated calcium channel alpha‐2 delta (α2δ) subunit mRNA‐containing cells in the rat central nervous system and the dorsal root ganglia , 2005 .

[26]  De-Pei Li,et al.  Regulation of synaptic inputs to paraventricular-spinal output neurons by alpha2 adrenergic receptors. , 2005, Journal of neurophysiology.

[27]  R. Santer,et al.  Anatomy and blood supply of the coeliac-superior mesenteric ganglion complex of the rat , 2004, Anatomy and Embryology.

[28]  David A Calhoun,et al.  Pathogenesis of Hypertension , 2003, Annals of Internal Medicine.

[29]  De-Pei Li,et al.  Angiotensin II Stimulates Spinally Projecting Paraventricular Neurons through Presynaptic Disinhibition , 2003, The Journal of Neuroscience.

[30]  A. Allen.  Inhibition of the Hypothalamic Paraventricular Nucleus in Spontaneously Hypertensive Rats Dramatically Reduces Sympathetic Vasomotor Tone , 2002, Hypertension.

[31]  J. Hang,et al.  Tissue-specific Expression and Gabapentin-Binding Properties of Calcium Channel α2δ Subunit Subtypes , 2001, The Journal of Membrane Biology.

[32]  N. Klugbauer,et al.  Calcium Channel α2δ Subunits—Structure and Gabapentin Binding , 2001 .

[33]  E. Pothos,et al.  Regulation of Quantal Size by Presynaptic Mechanisms , 2000, Reviews in the neurosciences.

[34]  C. Elger,et al.  Effects of Phenytoin, Carbamazepine, and Gabapentin on Calcium Channels in Hippocampal Granule Cells from Patients with Temporal Lobe Epilepsy , 1998, Epilepsia.

[35]  J. Offord,et al.  The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the Subunit of a Calcium Channel (*) , 1996, The Journal of Biological Chemistry.

[36]  R. Macdonald,et al.  Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons , 1993, Epilepsy Research.