Jon W. Johnson, PhD

Professor, Neuroscience, Psychiatry

Contact

458 Crawford Hall
412-624-4295
F: 412-624-4393
jjohnson@pitt.edu

Education

PhD, Stanford Univeristy (1986)

Focus

Biophysics, pharmacology, structure, and regulation of glutamate receptors.

Research Summary

Ion channels are fundamental to the movement and processing of information in all nervous systems, and therefore are attractive research subjects for neuroscientists. Ion channels are a fascinating research topic for additional reasons: they are beautifully evolved multifunctional machines that are both challenging and great fun to study. Professor Johnson's laboratory uses biophysical, electrophysiological, molecular, optical, pharmacological, and computational approaches to study the function, structure, and regulation of ion channels. We focus on channels involved in synaptic communication within vertebrate nervous systems.

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.

Summer Undergraduate Research Program

Yes

Publications

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.

 

Collaborations include computational modeling of NMDA receptor structure (with the group of Dr. Maria Kurnikova, Carnegie Mellon University) and development of new NMDA receptor channel blockers with improved neuroprotective properties (with the group of Dr. Santiago Vázquez, University of Barcelona).