Gucan Dai
Saint Louis University, MO·Biophysics
Electrical signals in the heart and nervous system depend on ion channels — proteins that open a pore in the cell membrane to let charged particles through. Many of these channels contain a voltage-sensing domain, a segment that physically moves when the voltage across the membrane changes and then pulls the pore open or shut.
- Fields
Biophysics
Pharmacology
Neuroscience
- Topics
ion channels
voltage sensing
HCN channels
- Grants
- 2 known grants, through May 2029
What they work on
- Determine how the voltage-sensing domain of hyperpolarization-activated HCN pacemaker channels moves during activation, including its intermediate conformations, using patch-clamp fluorometry on channels expressed in human cell lines.
- Test how long QT syndrome mutations in the S4 voltage-sensor helix of the hERG potassium channel alter voltage-dependent activation, and measure the underlying structural rearrangements with transition metal ion FRET (tmFRET) converted into interatomic distances.
- Define how regulatory domains, such as the cyclic-nucleotide-binding domain, control channel opening by reshaping voltage-sensor conformations, combining phasor-plot fluorescence lifetime imaging with molecular dynamics simulations.
- Test whether cholesterol-rich ordered membrane domains directly control the HCN channel voltage sensor and thereby neuronal excitability, using native HCN currents in somatosensory dorsal root ganglion neurons linked to neuropathic and inflammatory pain.
- Measure how lipid composition, ordered-domain localization and disease-associated mutations change the intermediate states of voltage sensors in native membranes, using site-specific labeling via noncanonical amino acids and click chemistry for FRET.
More about the research
How that movement happens, what intermediate shapes the sensor passes through, and how it is influenced by the surrounding membrane and by disease-causing mutations are open questions. Both projects here attack these questions with the same toolkit: recording electrical current from a single patch of membrane while simultaneously watching the channel protein change shape through fluorescence, so structure and function are measured at the same time in living cells.
Why it matters
Arrhythmias and sudden cardiac death from long QT syndrome, and chronic neuropathic and inflammatory pain, both trace back to ion channels opening at the wrong voltage. Pinning down how the voltage sensors of HCN and hERG channels move, and how membrane cholesterol-rich domains and inherited mutations change that movement, could identify new ways to tune pacemaker activity or nerve excitability and point to drug targets for arrhythmia and pain.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Bankston
University of Colorado Denver/Anschutz Medical Campus, CO·Biophysics
Determine how single-tail lipids, including polyunsaturated fatty acids, lysophosphatidyl cholines and N-acyl amino acids, bind to ASIC3, an acid-sensing ion channel, and how they boost or open it.
Christopher A Ahern
University of Iowa, IA·Biophysics
Develop light-activated photochemical 'stapling' to lock voltage-gated sodium, calcium and potassium channels into key shapes in live cell membranes before purification for structural determination.
Robert Piper
University of Iowa, IA·Physiology
Produce stably expressing human HEK cell lines that pair individual β subunits (Scn2b, Scn3b, Scn4b) with specific pore-forming NaV α subunits.
The school
Saint Louis University: 5 labs on PI Pages, $96M a year on research, 251 research doctorates a year.
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