ArticleThe Journal of physiology2018
α2δ-1 couples to NMDA receptors in the hypothalamus to sustain sympathetic vasomotor activity in hypertension.
Article in The Journal of physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- WNK-SPAK-NKCC1/KCC2 pathway disrupts chloride homeostasis and drives hyperactivation of PVN-CRH neurons in essential hypertension.iScience · 2026Article
- Cardiac α2δ1 C-terminal contributes to left atrial hypertrophy in chronic ischemic heart failure, in association with changes in membrane GluN1 and p-CAMKII/p-HDAC4 signaling.Cell and tissue research · 2026Article
- HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Role of Piezo1 Channels Expressed in PVN in Regulating Sympathetic Nerve Activity and Arterial Blood Pressure in Rats.International journal of molecular sciences · 2026Article
- α2δ-1-NMDAR1 complex in the hypothalamic paraventricular nucleus mediates anxiety-induced sympathetic hyperactivity.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- RCAN1-Mediated Calcineurin Impairment Drives Sympathetic Outflow in Hypertension.Circulation research · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Calcineurin regulates synaptic CaThe Journal of physiology · 2024Article
- DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development.The Journal of biological chemistry · 2024Article
- Article
- Brain α2δ-1-Bound NMDA Receptors Drive Calcineurin Inhibitor-Induced Hypertension.Circulation research · 2023Article
- Hypothalamic Corticotropin-Releasing Hormone Contributes to Hypertension in Spontaneously Hypertensive Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- NMDA Receptors at Primary Afferent-Excitatory Neuron Synapses Differentially Sustain Chemotherapy- and Nerve Trauma-Induced Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The α2δ-1-NMDA receptor complex and its potential as a therapeutic target for ischemic stroke.Frontiers in neurology · 2023Review
- α2δ-1 protein drives opioid-induced conditioned reward and synaptic NMDA receptor hyperactivity in the nucleus accumbens.Journal of neurochemistry · 2023Article
- Calcineurin Controls Hypothalamic NMDA Receptor Activity and Sympathetic Outflow.Circulation research · 2022Article
- Low-intensity blast induces acute glutamatergic hyperexcitability in mouse hippocampus leading to long-term learning deficits and altered expression of proteins involved in synaptic plasticity and serine protease inhibitors.Neurobiology of disease · 2022Article
- Protein Kinase C-Mediated Phosphorylation and α2δ-1 Interdependently Regulate NMDA Receptor Trafficking and Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- α2δ-1-Dependent NMDA Receptor Activity in the Hypothalamus Is an Effector of Genetic-Environment Interactions That Drive Persistent Hypertension.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
key pointsα2δ-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. ABSTRACT: Increased glutamate NMDA receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus leads to augmented sympathetic outflow in hypertension. However, the molecular mechanisms underlying this effect remain unclear. α2δ-1, previously considered to be a voltage-activated calcium channel subunit, is a newly discovered powerful regulator of NMDARs. In the present study, we determined the role of α2δ-1 in regulating synaptic NMDAR activity of rostral ventrolateral medulla (RVLM)-projecting PVN neurons in spontaneously hypertensive rats (SHRs). We show that the protein levels of α2δ-1 and NMDARs in synaptosomes and the α2δ-1-NMDAR complexes in the hypothalamus were substantially higher in SHRs than in normotensive control rats. The basal amplitude of evoked NMDAR currents and NMDAR-mediated synaptic glutamate release in RVLM-projecting PVN neurons were significantly increased in SHRs. Strikingly, inhibiting α2δ-1 activity with gabapentin or disrupting the α2δ-1-NMDAR association with an α2δ-1 C-terminus peptide completely normalized the amplitude of evoked NMDAR currents and NMDAR-mediated synaptic glutamate release in RVLM-projecting PVN neurons in SHRs. In addition, microinjection of the α2δ-1 C-terminus peptide into the PVN substantially reduced arterial blood pressure and renal sympathetic nerve discharges in SHRs. Our findings indicate that α2δ-1-bound NMDARs in the PVN are required for the potentiated presynaptic and postsynaptic NMDAR activity of PVN presympathetic neurons and for the elevated sympathetic outflow in hypertension. α2δ-1-bound NMDARs may be an opportune target for treating neurogenic hypertension.
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