21 / 119
Emerging Concepts in Ion Channel Biophysics
Wednesday Speaker Abstracts
16
Genetics and Physics of in vivo Mechanical Activation of Ion Channels
Miriam Goodman
.
Stanford University, Stanford, CA, USA.
Ion channels are the first responders of hearing, touch, proprioception and pain. They convert the
mechanical energy of sound, touch, movement, or tissue damage into neural signals. At least
three classes of proteins have been linked to the mechano-electrical transduction (MeT) channels
responsible for mechanosensation in mammals and invertebrates: DEG/ENaC/ASIC sodium
channels, TRP cation channels, and Piezo cation channels. We are working to determine the
protein partners that form native MeT channels and the physics of force transfer in skin-sensory
composite tissues. Our work focuses on DEG/ENaC/ASIC channels responsible for touch
sensation in C. elegans nematodes, leveraging genetic dissection, gene editing, cellular
neurophysiology, and tissue mechanobiology. Prior work identified two pore-forming and two
auxiliary subunits required to form native MeT channels in C. elegans touch receptor neurons
(TRNs). New results emerging from our lab and others are revising this view. We are
investigating DEGT-1 as a potential pore-forming subunit of native MeT channels. Like Pacinian
corpuscles and other rapidly adapting tactile sensors in vertebrates, the TRNs respond to
mechanical stimulation in a frequency-dependent manner. I will discuss our recent model of
frequency-dependence (Eastwood et al, PNAS, 2015), experimental tests of its predictions, and
implications for the expected properties of MeT channels in their native context versus the same
channels reconstituted in cells or lipid bilayers.
Acknowledgements: This work represents the current and prior effort of the presenter and a
research team, including Sylvia Fechner, Samata Katta, Amy L. Eastwood, Frederic Loizeau,
Sung-Jin Park, Bryan Petzold, Beth L. Pruitt, Alessandro Sanzeni, Massimo Vergassola. It is/has
been funded by NIH grants (R01EB006745, R01NS047715), NIH fellowships (F32NS065718 to
ALE, F31NS093825 to SK), NSF fellowship (Petzold) and fellowship funding from Swiss
National Science Foundation (Loizeau), Samsung Foundation (Park), and DFG (Fechner).