- PhD, Stanford University (1986)
Education & Training
The Johnson lab is involved in multiple collaborative projects incorporating electrophysiology, structural modeling, medicinal chemistry, and cutting-edge optical approaches to study properties and pharmacology of glutamate receptors.
Of particular interest to the laboratory are N-methyl-d-aspartate (NMDA) receptors, ligand-gated channels that are members of the ionotropic glutamate receptor family. Glutamate receptors mediate most fast excitatory synaptic transmission in vertebrate nervous systems. NMDA receptors are unusual receptors in many respects. Their unique combination of characteristics permit them to play pivotal roles in basic nervous system functions, including brain development and learning and memory. NMDA receptors are also involved in many nervous system disorders, including epilepsy, schizophrenia, ischemia, Alzheimer's disease, Huntington's disease, and depression.
We use whole-cell and single-channel patch clamp recordings of glutamate receptor currents in transfected cell lines, cultured neurons, and brain slices. Our ability to integrate study of glutamate receptor properties using native, wild-type recombinant, and mutant receptors with quantitative modeling at multiple levels affords broad insight into how receptors function. Our research addresses a wide range of topics, including basic aspects of receptor function (e.g., channel permeation, block, voltage dependence, and gating), the mechanism of action of therapeutic drugs, and the roles of NMDA receptors in activation of inhibitory interneurons. Ongoing projects include elucidation of a newly discovered route of inhibitor access to the channel of NMDA receptors, and examination of inhibitory mechanisms that contribute to the clinical efficacy of the Alzheimer’s drug memantine.
Wilcox, M.R., Nigam, A., Glasgow, N.G., Narangoda, C., Phillips, M.B., Patel, D.S., Mesbahi-Vasey, S., Turcu, A.L., Vázquez, S., Kurnikova, M.G., Johnson, J.W. (2022). Inhibition of NMDA receptors through a membrane-to-channel path. Nat. Commun. 13, 4114; doi: 10.1038/s41467-022-31817-z.
Turcu, A.L., Companys-Alemany, J., Phillips. M.B., Patel, D.S., Griñán-Ferréc, C., Loza, M.I., Brea, J.M., Pérez, B., Soto, D., Sureda, F.X., Kurnikova, M.G., Johnson, J.W., Pallàs, M. and Vázquez, S. (2022). Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer's disease. Eur. J. Med. Chem. 236, 114354; doi.org/10.1016/j.ejmech.2022.114354.
Krall, R.F., Moutal, A., Phillips, M.B., Asraf, H., Johnson, J.W., Khanna, R., Hershfinkel, M., Aizenman, E. and Tzounopoulos, T. (2020). Synaptic Zinc Inhibition of NMDA Receptors Depends on the Association of GluN2A with the Zinc Transporter ZnT1. Sci. Adv. 6, eabb1515; doi: 10.1126/sciadv.abb1515.
Phillips, M.B., Nigam, A., and Johnson, J.W. (2020). Interplay between gating and block of ligand-gated ion channels. Brain Sci. 10, 928; doi:10.3390/brainsci10120928.
Leiva, R., Phillips, M.B., Turcu, A.L., Gratacòs-Batlle, E., León-García, L., Sureda, F.X., Soto, D., Johnson, J.W., Vázquez, S. (2018). Pharmacological and electrophysiological characterization of novel NMDA receptor antagonists. ACS Chem. Neurosci. doi: 10.1021/acschemneuro.8b00154.
Glasgow, N.G., Wilcox, M.R. and Johnson, J.W. (2018). Effects of Mg2+ on recovery of NMDA receptors from inhibition by memantine and ketamine reveal properties of a second site. Neuropharmacol. 137, 344-358.
Glasgow, N.G., Povysheva, N.V., Azofeifa, A.M. and Johnson, J.W. (2017). Memantine and ketamine differentially alter NMDA receptor desensitization. J. Neurosci. 37, 9686-9704.
Mesbahi-Vasey, S., Veral, L., Yonkunas, M., Johnson, J.W. and Kurnikova, M.G. (2017). All atom NMDA receptor transmembrane domain model development and simulations in lipid bilayers and water. PLoS One 12, e0177686. doi: 10.1371/journal.pone.0177686.
Povysheva, N.V. and Johnson, J.W. (2016). Effects of memantine on the excitation-inhibition balance in prefrontal cortex. Neurobiology of Disease 96, 75-83.
