TMEM16A on Qube 384

TMEM16A (ANO1) is a Ca²⁺-activated Cl- channel (CaCC) that is involved in a plethora of physiological and pathophysiological conditions. The channel was suggested as a target for treatment of asthma, secretory diarrheas, and hypertension. TMEM16A is unique as its gating synergistically depends on voltage and cytosolic Ca²⁺ (Scudieri et al. 2012).
A robust and high-throughput electrophysiology assay for TMEM16A was long awaited, but progress was hampered by the fact that many automated patch clamp devices rely on the use of fluoride (F^–)in the internal solution to promote seal formation. However CaF₂ has very low solubility and the resulting precipitation limits the ability to control precisely the concentration of Ca⁺ in the internal solution.
We recently developed a novel approach to test the pharmacological inhibition of TMEM16A on Qube with following characteristics:

• Consistently high success rates (>80%)
• Low run down
• High degree of pharmacological reproducibility (consistent IC50 values of multiple runs)