Single shot diagnosis of ion channel dysfunction from assimilation of cell membrane dynamics

TL;DR

This paper presents a rapid, single-shot diagnostic method using data assimilation to identify ion channel dysfunctions in neurons, potentially improving neurological disease diagnosis and drug screening.

Contribution

The authors introduce a novel data assimilation approach that accurately estimates ion channel parameters from electrical activity, enabling quick diagnosis of channel alterations.

Findings

Reconstructed ionic currents within 11% accuracy

Correctly identified which ion channels were altered

Predicted effects of channel blockers accurately

Abstract

Many neurological diseases originate in the dysfunction of cellular ion channels. Their diagnosis presents a challenge especially when alterations in the complement of ion channels are a priori unknown. Current approaches based on voltage clamps lack the throughput necessary to identify the mutations causing changes in electrical activity. Here, we introduce a single-shot method for diagnosing changes in the complement of ion channels from changes in the electrical activity of a cell. We developed data assimilation (DA) to estimate the parameters of individual ion channels and from these parameters reconstruct the ionic currents of hippocampal CA1 neurons to within 11% of their actual value. DA correctly predicts which ionic current is altered and by how much after we blocked the BK, SK, A and HCN channels with selective antagonists of known potency. We anticipate our assay will transform the treatment of neurological disease through comprehensive diagnosis and drug screening.