Manual patch-clamp technique was used to evaluate channel pharmacology using cells transiently transfected with wild-type and V434L mutant channel.
The dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016). Small molecule drugs have been identified that rectify this protein misfolding (‘correctors’) and facilitate channel opening (‘potentiators’), thereby restoring CFTR-mediated Cl- efflux at the apical cell membrane and providing clinical improvement (Hanrahan et al. 2017).
Nevertheless, enhanced efficacy remains a key research goal, and evidence indicates that this could be achieved by combining correctors/potentiators with modulators of the ubiquitin proteasomal system (UPS) that regulates CFTR protein degradation (Borgo et al. 2022). There is growing interest in the development of novel treatments that utilise this dual-target approach; we therefore set out to demonstrate that we could:
Manual patch-clamp technique was used to evaluate channel pharmacology using cells transiently transfected with wild-type and V434L mutant channel.
The HESI Cardiac Safety Committee present results from an international ion channel research study that assessed the variability of hERG data generated using automated patch clamp platforms (QPatch 48, Qube 384 and the SyncroPatch 384i) across four different labs.