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nkoch1 2022-06-22 11:40:41 -04:00
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@ -360,7 +360,7 @@ Mutations in \Kv are associated with episodic ataxia type~1 (EA1) and have been
\section*{Discussion (3000 Words Maximum - Currently 2145)}
% \textit{The discussion section should include a brief statement of the principal findings, a discussion of the validity of the observations, a discussion of the findings in light of other published work dealing with the same or closely related subjects, and a statement of the possible significance of the work. Extensive discussion of the literature is discouraged.}\\
To compare the effects of changes to properties of ionic currents on neuronal firing of different neuron types, a diverse set of conductance-based models were simulated. Changes to single ionic current properties, as well as application of known episodic ataxia type~1 associated \Kv mutations showed consistent effects on the rheobase across cell types, whereas the effects on AUC of the steady-state fi-curve depend on cell type. Our results demonstrate that LOF and GOF on the biophysical level cannot be uniquely transfered to the level of neuronal firing. The effects depend on the properties of the other currents expressed in a cell and are therefore depending on cell type.
To compare the effects of changes to properties of ionic currents on neuronal firing of different neuron types, a diverse set of conductance-based models were simulated. Changes to single ionic current properties, as well as known episodic ataxia type~1 associated \Kv mutations showed consistent effects on the rheobase across cell types, whereas the effects on AUC of the steady-state fI-curve depend on cell type. Our results demonstrate that LOF and GOF on the biophysical level cannot be uniquely transfered to the level of neuronal firing. The effects depend on the properties of the other currents expressed in a cell and are therefore depending on cell type.
%Using a set of diverse conductance-based neuronal models, the effects of changes to properties of ionic currents on neuronal firing were determined to be heterogenous for the AUC of the steady state fI curve but more homogenous for rheobase. For a known channelopathy, episodic ataxia type~1 associated \Kv mutations, the effects on rheobase are consistent across model cell types, whereas the effects on AUC depend on cell type. Our results demonstrate that LOF and GOF on the biophysical level cannot be uniquely transfered to the level of neuronal firing. The effects depend on the properties of the other currents expressed in a cell and are therefore depending on cell type.