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Structure, Function and Modulation of Ion Channels

Our Lab

Dissecting ion channels with biophysical and chemical approaches

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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

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  • Wheat germ agglutinin-conjugated fluorescent pH sensors for visualizing proton fluxes

    Small-molecule fluorescent wheat germ agglutinin (WGA) conjugates are routinely used to demarcate mammalian plasma membranes, because they bind to the cell's glycocalyx. Here, we describe the derivatization of WGA with a pH-sensitive rhodamine fluorophore (pHRho; pKa = 7) to detect proton channel fluxes and extracellular proton accumulation and depletion from primary cells. We found that WGA-pHRho labeling was uniform and did not appreciably alter the voltage gating of glycosylated ion channels,...
All Publications

 

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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.