Structure, Function and Modulation of Ion Channels

The Lab

Kobertz LabDissecting ion channels with biophysical and chemical approaches

Our laboratory investigates the glycosylation, assembly, structure, trafficking and function of ion channel complexes. We rely on traditional electrophysiological, biochemical, and imaging modalities, but we also design, develop, and utilize novel chemical tools to interrogate a wide variety of ion channels and membrane transport proteins responsible for cardiac and neuronal function. Thus, we have synthetic organic chemists, glycobiologists, membrane protein biochemists, and electrophysiologists working together to elucidate the molecular underpinnings of these membrane transport proteins in both healthy and diseased tissues.

 Meet the Lab

 

 

Research Focus

Exploiting the cell's glycocalyx to visualize extracellular fluxes

Given the laboratory's enthusiasm for studying ion channels, our lab has been developing a new approach to visualize ions exiting and entering cells. Our first publication in Cell Chemical Biology enabled the visualization of proton accumulation and depletion on the extracellular side of the membrane. Proton fluxes were visualized from voltage-gated ion channels, transporters, and mutant channels harboring mutations associated with human disease. The video (left) shows protons rushing into a cell after the channels were opened with hyperpolarizing pulse (-120 mV). The initial fluorescent signal is due to protonated fluorescent sensors covalently attached to the cell's glycocalyx. Proton channel activation at -120 mV results in proton depletion and loss of the fluorescent signal, which slowly returns after the channels are closed (30 mV).

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Publications

Kobertz Publications

Total: 1 results
  • Mutant SOD1 protein increases Nav1.3 channel excitability.

    Related Articles

    Mutant SOD1 protein increases Nav1.3 channel excitability.

    J Biol Phys. 2016 Jun;42(3):351-70

    Authors: Kubat Öktem E, Mruk K, Chang J, Akin A, Kobertz WR, Brown RH

    Abstract
    Amyotrophic lateral sclerosis (ALS) is a lethal paralytic disease caused by the degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) are present in ~20% of familial ALS and ~2% of all ALS cases. The most common SOD1 gene mutation in North America is a missense mutation substituting valine for alanine (A4V). In this study, we analyze sodium channel currents in oocytes expressing either wild-type or mutant (A4V) SOD1 protein. We demonstrate that the A4V mutation confers a propensity to hyperexcitability on a voltage-dependent sodium channel (Nav1.3) mediated by heightened total Na(+) conductance and a hyperpolarizing shift in the voltage dependence of Nav1.3 activation. To estimate the impact of these channel effects on excitability in an intact neuron, we simulated these changes in the program NEURON; this shows that the changes induced by mutant SOD1 increase the spontaneous firing frequency of the simulated neuron. These findings are consistent with the view that excessive excitability of neurons is one component in the pathogenesis of this disease.

    PMID: 27072680 [PubMed - indexed for MEDLINE]

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Contact Us

Office:
Lazare Research Building 804
Campus Map (pdf)

Phone:
508.856.8861 (office)
508.856.6722 (lab)

Email:
William.Kobertz@umassmed.edu

Mailing Address:
William R. Kobertz, Ph.D.
Department of Biochemistry and Molecular Pharmacology
University of Massachusetts Medical School
364 Plantation Street LRB804, Worcester, MA 01605-4321

Join Us

We are always interested in applications from qualified candidates at the postdoctoral and research associate levels. UMMS GSBS graduate students interested in rotating in the Kobertz Lab should email Dr. Kobertz to set up an appointment.

Undergraduates interested in pursuing a PhD at UMass Medical School should apply directly to the Graduate School of Biomedical Sciences Program.

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