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nkoch1 2022-05-09 11:18:52 -04:00
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@ -170,6 +170,7 @@ Voltage-gated ion channels are vital in determining neuronal excitability, actio
\notenk{Are there any obvious citations missing from the following section?}
The effects of channelopathies on ionic current kinetics are frequently assessed by transfection of heterologous expression systems without endogenous currents \citep{Balestrini1044, Noebels2017, Dunlop2008}, and are frequently classified as either a loss of function (LOF) or a gain of function (GOF) with respect to \textcolor{green}{changes in }the \textcolor{green}{amount of} ionic current \citep{Musto2020, Kullmann2002, Waxman2011}. \notenk{Do you think we need to discuss LOF and GOF more than this?} \notels{LOF and GOF are usually not explained in detail, I would think it's fine} These classes can be used to make rough estimates of the effects on neuronal firing \textcolor{red}{(papers?)}, which is important for understanding the pathophysiology of these disorders and for identification of potential therapeutic targets \citep{Orsini2018, Yang2018}. Experimentally, the effects of channelopathies on neuronal firing can be assessed using primary neuronal cultures \citep{Scalmani2006, Smith2018, Liu2019} or \textit{in vitro} recordings from transgenic mouse lines \citep{Mantegazza2019, Xie2010,Lory2020, Habib2015, Hedrich2019}.
%However the effect of a given channelopathy on different neuronal types across the brain is often unclear and not feasible to experimentally obtain. This is especially true when large numbers of distinct mutations are present and personalized medicine approaches are desired.
%Linking the effects of modified currents to neuronal firing is crucial for understanding the disease and finding possible treatments. There are many widely accepted approaches. Transfection of heterologous expression systems without endogenous currents reveals changes in ionic current kinetics \textcolor{red}{(cite some stuff)}. Simulations of these effects can predict their effect on neuronal firing \textcolor{red}{(cite some stuff)}. Or the influence on firing behaviour can be directly measured in transfected primary neuronal cultures \textcolor{red}{(cite some stuff)} or in brain slice recordings of mouse lines \textcolor{red}{(cite some stuff)}.