Single shot diagnosis of ion channel dysfunction from assimilation of cell membrane dynamics
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arXiv
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| Hauptverfasser: | , , , |
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| Format: | Preprint |
| Veröffentlicht: |
2023
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| _version_ | 1866916815897100288 |
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| author | Morris, Paul G Taylor, Joseph D. Paton, Julian F. R. Nogaret, Alain |
| author_facet | Morris, Paul G Taylor, Joseph D. Paton, Julian F. R. Nogaret, Alain |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2307_09877 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | Single shot diagnosis of ion channel dysfunction from assimilation of cell membrane dynamics Morris, Paul G Taylor, Joseph D. Paton, Julian F. R. Nogaret, Alain Quantitative Methods Biological Physics 49M29, 49M37 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. |
| title | Single shot diagnosis of ion channel dysfunction from assimilation of cell membrane dynamics |
| topic | Quantitative Methods Biological Physics 49M29, 49M37 |
| url | https://arxiv.org/abs/2307.09877 |