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nkoch1 2022-12-06 13:42:11 -05:00
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@ -210,7 +210,7 @@ Ion channel variants are frequently classified in heterologous expression system
Taken together, these examples demonstrate the need to study the effects of ion channel mutations in many different cell types --- a daunting if not impossible experimental challenge. In the context of this diversity, simulations of conductance-based neuronal models are a powerful tool bridging the gap between altered ionic currents and firing in a systematic and efficient way. Furthermore, simlutions allow to predict the potential effects of drugs needed to alleviate the pathophysiology of the respective mutation \citep{johannesen_genotype-phenotype_2021, lauxmann_therapeutic_2021, Bayraktar}.
In this study, we therefore investigated how the outcome of ionic current kinetic changes on firing depend on neuronal cell type by (1) characterizing firing responses with 2 measures, (2) simulating the response of a repertoire of different neuronal models to changes in single current parameters as well as (3) to more complex changes as they were observed for specific \textit{KCNA1} mutations that are associated with episodic ataxia type~1 \citep{Browne1994, Browne1995, lauxmann_therapeutic_2021}.
In this study, we therefore investigated how the outcome of ionic current kinetic changes on firing depend on neuronal cell type by (1) characterizing firing responses with 2 measures, (2) simulating the response of a repertoire of different neuronal models to changes in single current parameters as well as (3) to more complex changes \textcolor{red}{in this case} as they were observed for specific \textit{KCNA1} mutations that are associated with episodic ataxia type~1 \citep{Browne1994, Browne1995, lauxmann_therapeutic_2021}.
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%The effects of mutations in ion channel genes on ionic current kinetics are frequently assessed using heterologous expression systems without endogenous currents \citep{Balestrini1044, Noebels2017, Dunlop2008}.