11. - 14.09.2022 | The 31st Meeting of the Association Canaux Ionique
Centre de vacances du Lazaret - Le Lazaret
Go to the Conference website here.
Meet Dr. Conrad Weichbrodt and Nicoletta Murciano
Dr. Conrad Weichbrodtand Senior Scientist / Product Manager Orbit family, and Nicoletta Murciano Ph.D Student will be present. Join them at the booth and at the poster presentation session.
Presenter: Nicoletta Murciano
Title: Mechanical and Pharmacological Activation of Piezo1 Channels Characterized by High Throughput Electrophysiology
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 throughput 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 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 of PIEZO1 activation by fluid flow, Yoda1 (a small-molecule PIEZO1 agonist), 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, and British Heart Foundation, and has received funding from the European Union’s Horizon 2020 research and innovation program.
About the Association Canaux Ionique
The Ion Channel association is a non-profit association promoting scientific exchanges in the field of ion channels. Since 1989, the Ion Channel association has organized an international yearly meeting to gather ion channels researchers.
Membership is granted to those attending the ion channel meeting. The meeting organizing committee is renewed by half every year, each member being elected by a general assembly for two years. Members cannot be re-elected, except for the board. Each year, newly elected members are in charge of the organization of the five symposia of the meeting and invite speakers who are international leaders in their field. Older members organize the sponsoring and the logistics.