High-throughput automated patch-clamp analysis reveals altered excitability and variation of ion channel activity in ALS iPSC-derived motor neurons

Poster - High-throughput automated patch-clamp analysis reveals altered excitability and variation of ion channel activity in ALS iPSC-derived motor neurons

Abstract

The SyncroPatch 384 can be used to biophysically characterize iPSC-derived motor neurons to record voltage – and ligand-gated ion channels as well as APs in the current clamp mode with the possibility to record ionic conductance and cellular excitability within the same cell and/or at body temperature (3,4).

Comparison Nav, Kv and GABA channels reveal differences in current densities and activation/inactivation properties, suggesting ion channel remodeling within the ALS donor derived phenotype vs healthy donor cells.

Possible dysfunctional membrane excitability was shown in a reduced propensity of AP generation in patch clamp for ALS donor-derived cells that was further confirmed by irregular, high-frequency Ca2+ transients.

A loss of action potential output in patient-derived iPSC cells carrying the C9ORF72 ALS mutation has been suggested to contribute to downstream degenerative pathways that ultimately lead to loss in ALS.