Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Wednesday Speaker Abstracts

Magnetic Force Probing of Mechanically-activated Piezo Ion Channels Jorg Grandl . Duke University, Durham, NC, USA.

In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. However, many aspects of Piezo function remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function. We asked what specific parts (domains) of Piezo channels sense mechanical stimulation. To probe Piezos with sub-molecular resolution we developed a novel approach where we label specific domains within Piezos with magnetic nanoparticles and use an external magnetic field to generate a precise mechanical force that is highly localized within the channel protein. Simultaneously, we measure Piezo activation electrophysiologically. These experiments identified two distinct domains as being mechanically sensitive and involved in channel inactivation and activation.

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