Development and validation of a TRPML1 assay on an automated patch clamp platform

TRPML1 is a cation-selective ion channel ubiquitously expressed in lysosomes and late endosomes. TRPML1 is intimately involved in the regulation of lysosomal Ca2+ homeostasis and is consequently a critical component of autophagy and lysosomal biogenesis. Malfunctions of these processes are linked to various neurodegenerative disorders, including Alzheimer`s and Parkinson`s disease. The relevance of TRPML1 in neurodegenerative disorders is further validated by a loss-of-function mutation that was shown to cause the neurodegenerative lysosomal storage disease mucolipidosis type IV (MLIV).

The patch clamp technique remains the gold standard for studying ion channels as recordings directly measure the protein’s activity. Whilst powerful, the conventional patch clamp method requires highly trained scientists and allows only a low throughput. Automated patch clamp systems have evolved to overcome these limitations. These platforms are, therefore, well-suited to test large numbers of compounds quickly to support ion channel drug development programs.