Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Wednesday Speaker Abstracts

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).

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