Jon W. Johnson, Ph.D.
Professor, Neuroscience, Psychiatry- Ph.D. Stanford Univeristy (1986)
- Office: 458 Crawford Hall
- Telephone:412-624-4295
- Fax:412-624-4393
- E-mail: jjohnson@pitt.edu
- Website:
Biophysics, pharmacology, 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 remarkably well-designed 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 the vertebrate nervous system.
Of particular interest to the laboratory are N-methyl-D-aspartate (NMDA) receptors, ligand-gated channels that are members of the glutamate receptor family of ion channels. Glutamate receptors mediate most of the fast excitatory synaptic transmission in vertebrate nervous systems. NMDA receptors are unusual receptors in many respects. Their unusual 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, and a variety of neurodegenerative diseases.
We use whole-cell and single-channel patch clamp recordings from cultured neurons and transfected cell lines to investigate permeation, block, and gating of the channel of NMDA receptors. The ability to integrate measurements of cellular and single-channel activity mediated by native, wild-type recombinant, and mutant receptors allows us to gain particularly broad insight into how receptors work. Quantitative modeling is used to further deepen understanding of receptor function. Our research provides insight into the mechanisms by which NMDA receptors contribute to both normal function and dysfunction of the nervous system.
An additional research focus of the lab is modulation of synaptic glutamate responses by glutamate itself. This form of regulation is involved in, for example, the widely studied phenomena of long-term potentiation and long-term depression. We are examining postsynaptic modulatory mechanisms by combining focal application of exogenous glutamate with whole-cell recordings of visually identified neurons in brain slices.
Selected Publications:
Gielen, M., Retchless, B.S., Mony, L., Johnson, J.W., and Paoletti, P. Mechanism of differential control of NMDA receptor activity by NR2 subunits. Nature 459,703-707, 2009.
Kotermanski, S.E., and Johnson, J.W. Mg2+ imparts NMDA receptor subtype selectivity to the Alzheimer’s drug memantine. J. Neurosci. 29, 2774-2770, 2009.
Clarke, R.J., and Johnson, J.W. Voltage-dependent gating of NR1/2B NMDA receptors. J. Physiol. 586, 5727-5741, 2008.
Gielen, M., Le Goff, A., Stroebel, D., Johnson, J.W., Neyton, J., and Paoletti, P. Structural rearrangements of NR1/NR2A NMDA receptors during allosteric inhibition. Neuron 57, 80-93, 2008.
Qian, A., and Johnson, J.W. Permeant ion effects on external Mg2+ block of NR1/2D NMDA receptors. J. Neurosci. 26, 10899-10910, 2006.