GABAergic neurotransmission depends upon the transmembrane Cl concentration gradient that exists at the synapse. The intracellular Cl concentration in CNS and PNS neurons is regulated, in part, by cation-chloride cotransport mechanisms such as Na-K-2Cl and K-Cl cotransporters. For example, the inward Na-K-2Cl cotransporter is highly expressed in immature CNS neurons, resulting in a high intracellular Cl- concentration and GABA depolarizing or excitatory responses. In contrast, mature CNS neurons have low Na-K-2Cl cotransporter and high K-Cl cotransporter leading to low intracellular Cl- and GABA hyperpolarizing or inhibitory responses. Our laboratory is creating knockouts of the cotransporters and studying their relationship with neurotransmission and behavior. Our work, in collaboration with Drs. Robert MacDonald and Mike McDonald, involves molecular biology, physiology, electrophysiology and behavior. These studies have significance in perception of pain, hyper-excitability and epilepsy, nerve conduction, peripheral neuropathy and paraplegia.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. A dileucine motif in the COOH-terminal domain of NKCC1 targets the cotransporter to the plasma membrane. Koumangoye R, Omer S, Delpire E (2019) Am J Physiol Cell Physiol 316(4): C545-C558
    › Primary publication · 30865516 (PubMed) · PMC6482672 (PubMed Central)
  2. Elusive role of the Na-K-2Cl cotransporter in the choroid plexus. Delpire E, Gagnon KB (2019) Am J Physiol Cell Physiol 316(4): C522-C524
    › Primary publication · 30576234 (PubMed) · PMC6482669 (PubMed Central)
  3. Agmatine preferentially antagonizes GluN2B-containing N-methyl-d-aspartate receptors in spinal cord. Waataja JJ, Peterson CD, Verma H, Goracke-Postle CJ, Séguéla P, Delpire E, Wilcox GL, Fairbanks CA (2019) J Neurophysiol 121(2): 662-671
    › Primary publication · 30427758 (PubMed) · PMC6397392 (PubMed Central)
  4. Preface. Levitan I, Delpire E (2018) Curr Top Membr : xv-xvii
    › Primary publication · 30243443 (PubMed)
  5. Water Homeostasis and Cell Volume Maintenance and Regulation. Delpire E, Gagnon KB (2018) Curr Top Membr : 3-52
    › Primary publication · 30243436 (PubMed) · PMC6457474 (PubMed Central)
  6. Genetic loss of GluN2B in D1-expressing cell types enhances long-term cocaine reward and potentiation of thalamo-accumbens synapses. Joffe ME, Turner BD, Delpire E, Grueter BA (2018) Neuropsychopharmacology 43(12): 2383-2389
    › Primary publication · 29982266 (PubMed) · PMC6180117 (PubMed Central)
  7. Mistargeting of a truncated Na-K-2Cl cotransporter in epithelial cells. Koumangoye R, Omer S, Delpire E (2018) Am J Physiol Cell Physiol 315(2): C258-C276
    › Primary publication · 29719172 (PubMed) · PMC6139505 (PubMed Central)
  8. Na -K -2Cl Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia. Delpire E, Gagnon KB (2018) Compr Physiol 8(2): 871-901
    › Primary publication · 29687903 (PubMed)
  9. Mechanism of Hyperkalemia-Induced Metabolic Acidosis. Harris AN, Grimm PR, Lee HW, Delpire E, Fang L, Verlander JW, Welling PA, Weiner ID (2018) J Am Soc Nephrol 29(5): 1411-1425
    › Primary publication · 29483157 (PubMed) · PMC5967781 (PubMed Central)
  10. A role for KCC3 in maintaining cell volume of peripheral nerve fibers. Flores B, Schornak CC, Delpire E (2019) Neurochem Int : 114-124
    › Primary publication · 29366908 (PubMed) · PMC6398598 (PubMed Central)
  11. DNPEP is not the only peptidase that produces SPAK fragments in kidney. Koumangoye R, Delpire E (2017) Physiol Rep 5(21)
    › Primary publication · 29122955 (PubMed) · PMC5688775 (PubMed Central)
  12. AJP-Cell Physiology begins landmark reviews in cell physiology: an editorial from the senior editors of AJP-Cell Physiology. Delpire E, Hamilton KL, Hawke TJ, Isenberg JS, Lotersztajn S, Yuan JX, Adams JC (2018) Am J Physiol Cell Physiol 314(1): C1-C2
    › Primary publication · 29092820 (PubMed) · PMC6334934 (PubMed Central)
  13. Implications of the N-terminal heterogeneity for the neuronal K-Cl cotransporter KCC2 function. Markkanen M, Ludwig A, Khirug S, Pryazhnikov E, Soni S, Khiroug L, Delpire E, Rivera C, Airaksinen MS, Uvarov P (2017) Brain Res : 87-101
    › Primary publication · 28888841 (PubMed)
  14. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, Vera A, DiLuna ML, Delpire E, Alper SL, Gunel M, Gerzanich V, Medzhitov R, Simard JM, Kahle KT (2017) Nat Med 23(8): 997-1003
    › Primary publication · 28692063 (PubMed)
  15. Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport. Zhang J, Karimy JK, Delpire E, Kahle KT (2017) Expert Opin Ther Targets 21(8): 795-804
    › Primary publication · 28679296 (PubMed) · PMC6081737 (PubMed Central)
  16. KCC3 loss-of-function contributes to Andermann syndrome by inducing activity-dependent neuromuscular junction defects. Bowerman M, Salsac C, Bernard V, Soulard C, Dionne A, Coque E, Benlefki S, Hince P, Dion PA, Butler-Browne G, Camu W, Bouchard JP, Delpire E, Rouleau GA, Raoul C, Scamps F (2017) Neurobiol Dis : 35-48
    › Primary publication · 28647557 (PubMed)
  17. Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules. Grimm PR, Coleman R, Delpire E, Welling PA (2017) J Am Soc Nephrol 28(9): 2597-2606
    › Primary publication · 28442491 (PubMed) · PMC5576927 (PubMed Central)
  18. Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential. Glykys J, Dzhala V, Egawa K, Kahle KT, Delpire E, Staley K (2017) Trends Neurosci 40(5): 276-294
    › Primary publication · 28431741 (PubMed) · PMC5473173 (PubMed Central)
  19. WNK Kinase Signaling in Ion Homeostasis and Human Disease. Shekarabi M, Zhang J, Khanna AR, Ellison DH, Delpire E, Kahle KT (2017) Cell Metab 25(2): 285-299
    › Primary publication · 28178566 (PubMed)
  20. Reduced ethanol drinking following selective cortical interneuron deletion of the GluN2B NMDA receptors subunit. Radke AK, Jury NJ, Delpire E, Nakazawa K, Holmes A (2017) Alcohol : 47-51
    › Primary publication · 28109345 (PubMed) · PMC5444088 (PubMed Central)
  21. The mysterious role of the neuronal anion exchanger-3. Delpire E (2017) J Physiol 595(3): 601-602
    › Primary publication · 28097651 (PubMed) · PMC5285717 (PubMed Central)
  22. The KCC3 cotransporter as a therapeutic target for peripheral neuropathy. Delpire E, Kahle KT (2017) Expert Opin Ther Targets 21(2): 113-116
    › Primary publication · 28019725 (PubMed)
  23. Challenges of Finding Novel Drugs Targeting the K-Cl Cotransporter. Delpire E, Weaver CD (2016) ACS Chem Neurosci 7(12): 1624-1627
    › Primary publication · 27998063 (PubMed) · PMC5473358 (PubMed Central)
  24. A patient with multisystem dysfunction carries a truncation mutation in human , the gene encoding the Na-K-2Cl cotransporter, NKCC1. Delpire E, Wolfe L, Flores B, Koumangoye R, Schornak CC, Omer S, Pusey B, Lau C, Markello T, Adams DR (2016) Cold Spring Harb Mol Case Stud 2(6): a001289
    › Primary publication · 27900370 (PubMed) · PMC5111002 (PubMed Central)
  25. KCC3 deficiency-induced disruption of paranodal loops and impairment of axonal excitability in the peripheral nervous system. Sun YT, Tzeng SF, Lin TS, Hsu KS, Delpire E, Shen MR (2016) Neuroscience : 91-102
    › Primary publication · 27568057 (PubMed)
  26. The KCC2 Cotransporter and Human Epilepsy: Getting Excited About Inhibition. Kahle KT, Khanna AR, Duan J, Staley KJ, Delpire E, Poduri A (2016) Neuroscientist 22(6): 555-562
    › Primary publication · 27130838 (PubMed)
  27. The Ste20 kinases SPAK and OSR1 travel between cells through exosomes. Koumangoye R, Delpire E (2016) Am J Physiol Cell Physiol 311(1): C43-53
    › Primary publication · 27122160 (PubMed) · PMC4967142 (PubMed Central)
  28. STIM and Orai Proteins in Calcium Signaling: an AJP-Cell Physiology series of Themed Reviews. Delpire E (2016) Am J Physiol Cell Physiol 310(6): C401
    › Primary publication · 26979414 (PubMed)
  29. Hyperpolarization-independent maturation and refinement of GABA/glycinergic connections in the auditory brain stem. Lee H, Bach E, Noh J, Delpire E, Kandler K (2016) J Neurophysiol 115(3): 1170-82
    › Primary publication · 26655825 (PubMed) · PMC4808136 (PubMed Central)
  30. Research antibodies: do not use them to stain your reputation. Delpire E (2015) Am J Physiol Cell Physiol 309(11): C707-8
    › Primary publication · 26628686 (PubMed) · PMC4725442 (PubMed Central)
  31. Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression. Wills TA, Baucum AJ, Holleran KM, Chen Y, Pasek JG, Delpire E, Tabb DL, Colbran RJ, Winder DG (2017) Addict Biol 22(2): 275-290
    › Primary publication · 26549202 (PubMed) · PMC4860359 (PubMed Central)
  32. Kinase-KCC2 coupling: Cl- rheostasis, disease susceptibility, therapeutic target. Kahle KT, Delpire E (2016) J Neurophysiol 115(1): 8-18
    › Primary publication · 26510764 (PubMed) · PMC4760510 (PubMed Central)
  33. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis. Üner A, Gonçalves GH, Li W, Porceban M, Caron N, Schönke M, Delpire E, Sakimura K, Bjørbæk C (2015) Mol Metab 4(10): 678-91
    › Primary publication · 26500840 (PubMed) · PMC4588453 (PubMed Central)
  34. K-Cl cotransporters, cell volume homeostasis, and neurological disease. Kahle KT, Khanna AR, Alper SL, Adragna NC, Lauf PK, Sun D, Delpire E (2015) Trends Mol Med 21(8): 513-23
    › Primary publication · 26142773 (PubMed) · PMC4834970 (PubMed Central)
  35. Integrated compensatory network is activated in the absence of NCC phosphorylation. Grimm PR, Lazo-Fernandez Y, Delpire E, Wall SM, Dorsey SG, Weinman EJ, Coleman R, Wade JB, Welling PA (2015) J Clin Invest 125(5): 2136-50
    › Primary publication · 25893600 (PubMed) · PMC4463200 (PubMed Central)

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    Keywords & MeSH Terms

    MeSH terms are retrieved from PubMed records. Learn more.

    Key: MeSH Term Keyword

    Action Potentials Adolescent Agenesis of Corpus Callosum Amiloride Amino Acid Sequence Antibodies Brain Edema Carbonic Anhydrases Cell Physiological Phenomena Choroid Plexus Coculture Techniques Endocrine System Fibroblasts gamma-Aminobutyric Acid Gene Deletion HeLa Cells Hyperkalemia Ions Locomotion Molecular Neurophysiology Natriuresis Nociception Oocytes Peptide Fragments Protein Isoforms Proteome Receptors, Metabotropic Glutamate Salivary Glands Solute Carrier Family 12, Member 3 Spinal Cord Thiocarbamates