Biophysical models reveal the relative importance of transporter proteins and impermeant anions in chloride homeostasis. Düsterwald, K., M., Currin, C., B., Burman, R., J., Akerman, C., J., Kay, A., R., & Raimondo, J., V. eLife, 9, 2018.
Biophysical models reveal the relative importance of transporter proteins and impermeant anions in chloride homeostasis [link]Website  doi  abstract   bibtex   2 downloads  
Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl- ions based on the neuronal Cl- driving force. Established theories regarding the determinants of Cl- driving force have recently been questioned. Here, we present biophysical models of Cl- homeostasis using the pump-leak model. Using numerical and novel analytic solutions, we demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl- driving force. Our models, together with experimental validation, show that while impermeant anions can contribute to setting [Cl-]i in neurons, they have a negligible effect on the driving force for Cl- locally and cell-wide. In contrast, we demonstrate that CCCs are well-suited for modulating Cl- driving force and hence inhibitory signaling in neurons. Our findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.
@article{
 title = {Biophysical models reveal the relative importance of transporter proteins and impermeant anions in chloride homeostasis},
 type = {article},
 year = {2018},
 volume = {7},
 websites = {https://elifesciences.org/articles/39575},
 month = {9},
 day = {27},
 id = {ef06980f-e4cf-3cb9-a7e5-ce73c209b9e8},
 created = {2018-10-27T20:40:55.303Z},
 accessed = {2018-10-27},
 file_attached = {true},
 profile_id = {14badb0b-89a9-3047-a69a-683d5240354c},
 last_modified = {2019-10-31T15:55:19.149Z},
 read = {true},
 starred = {false},
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 citation_key = {Dusterwald2018},
 folder_uuids = {bf6cbabe-7a6a-4003-9dd0-f1c24e66ab8a},
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 abstract = {Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl- ions based on the neuronal Cl- driving force. Established theories regarding the determinants of Cl- driving force have recently been questioned. Here, we present biophysical models of Cl- homeostasis using the pump-leak model. Using numerical and novel analytic solutions, we demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl- driving force. Our models, together with experimental validation, show that while impermeant anions can contribute to setting [Cl-]i in neurons, they have a negligible effect on the driving force for Cl- locally and cell-wide. In contrast, we demonstrate that CCCs are well-suited for modulating Cl- driving force and hence inhibitory signaling in neurons. Our findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.},
 bibtype = {article},
 author = {Düsterwald, Kira M and Currin, Christopher B and Burman, Richard J and Akerman, Colin J and Kay, Alan R and Raimondo, Joseph V},
 doi = {10.7554/eLife.39575},
 journal = {eLife}
}
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