10. - 15.07.2022 | Ion Channels Gordon Research Conference
Conference Venue: Mount Holyoke College, South Hadley, MA, United States
Go to the Conference website here.
Meet Andrea Brüggemann and Nicoletta Murciano
Nanion CSO, Andrea Brüggemann will be giving a talk.
Saturday, July 11th, 2022
Time slot: 8 PM - 8:20 PM CEST
Title: "Mechanical and Pharmacological Activation of Piezo1 Channels Characterized by High Throughput Electrophysiology"
Additionally, the following poster will be presented:
Presenter: Nicoletta Murciano
Title: Mechanical and Pharmacological Activation of Piezo1 Channels Characterized by High Throughput Electrophysiology
PIEZO channels are mechanically-activated cation channels that PIEZO channels are mechanically-activated cation channels that play important roles in biological functions including touch, proprioception, shear stress and stretch sensation as well as blood pressure regulation. Mutations in Homo sapiens PIEZO1 channels are associated with anemia, malarial resistance, lymphatic dysplasia and varicose vein disease, suggesting important red blood cells and vascular roles in humans. The pharmacology of the PIEZO1 channels is in its infancy. Here we sought high throughout methodology for investigating small-molecule modulation in combination with mechanical stimulation. A bottleneck in PIEZO drug development has been the lack of mechanical stimulation in automated patch clamp. Here we show how the optimization of pipetting parameters and the modification of the NPC-384 chip of the SyncroPatch 384 lead to the possibility to mechanically stimulate PIEZO1 channels using high throughput electrophysiology. Data of mouse and human PIEZO1 channels expressed in HEK T-REX 293 cells activated by either mechanical or chemical stimuli will be shown as well as the combination of both methods. Under voltage-clamp, we were able to show reliable quantification ofPIEZO1 activation by fluid flow, Yoda1 (a small-molecule PIEZO1agonist) and a Yoda1 analogue. To our knowledge, this is the first time that mechanical stimulation of PIEZO channels in a high throughput planar patch clamp system has been shown. The possibility of comparing and combining mechanical and chemical stimulation in a high throughput electrophysiological assay facilitates the biophysical and pharmacological studies of PIEZO channels. This work was supported by research grants from the Wellcome Trust, British Heart Foundation and has received funding from the European Union’s Horizon 2020 research and innovation program.
About the Ion Channels Gordon Research Conference
The guiding principle of this conference is to convene and highlight the latest advances in our understanding of ion channel structure, physiological roles of channels, ion channel defects that underlie disease, and potential treatment strategies. The 2022 iteration of the Ion Channels GRC will turn toward the roles of ion channels in health and disease, with sessions organized around advances in our understanding of structure, function, and diseases related to the spectrum of ion channels. Our diverse panel of speakers and discussion leaders are selected to maximize the perspectives presented, with approaches ranging from cryo-electron microscopy of channels and complexes to behavioral studies of model organisms engineered to recapitulate human disease phenotypes. Ideally these sessions will pique the curiosity of the diverse makeup of the audience, and stimulate lively discussion among all participants. In addition, scientific discussion will be facilitated and promoted at four poster sessions throughout the week, so that all meeting attendees will have the opportunity to make scientific connections that are critical to moving the field forward. Although “Ion Channels” is a long-standing and well established conference, we uphold a tradition of bringing new speakers and young investigators front-and-center, for presentation of new ideas and discoveries, with many opportunities for interaction among students and researchers at all career stages in the most collegial setting.