changed minor things in discussion

manuscript.tex

@@ -265,7 +265,7 @@ Alterations in gating \(V_{1/2}\) and slope factor k as well as the current cond
 \end{figure}
 
 \subsection*{\Kv}
-Mutations in \Kv are associated with episodic ataxia type 1 (EA1) have been characterized biophysically and are used here as a case study in the effects of current environment on the outcomes of channelopathies on firing. The changes in AUC and rheobase from wild-type values for reported EA1 associated \Kv mutations are heterogenous across models containing \Kv, but generally show decreases in rheobase (\Cref{fig:simulation_model_comparision}A-I).  Pairwise non-parametric Kendall \(\tau\) rank correlations between the simulated effects of these \Kv mutations on rheobase are highly correlated across models (\Cref{fig:simulation_model_comparision}J). However, the effects of the \Kv mutations on AUC are more heterogenous as reflected by both weak and strong positive and negative pairwise correlations between models (\Cref{fig:simulation_model_comparision}K).
+Mutations in \Kv are associated with episodic ataxia type 1 (EA1) have been characterized biophysically and are used here as a case study in the effects of current environment on the outcomes of channelopathies on firing. The changes in AUC and rheobase from wild type values for reported EA1 associated \Kv mutations are heterogenous across models containing \Kv, but generally show decreases in rheobase (\Cref{fig:simulation_model_comparision}A-I).  Pairwise non-parametric Kendall \(\tau\) rank correlations between the simulated effects of these \Kv mutations on rheobase are highly correlated across models (\Cref{fig:simulation_model_comparision}J). However, the effects of the \Kv mutations on AUC are more heterogenous as reflected by both weak and strong positive and negative pairwise correlations between models (\Cref{fig:simulation_model_comparision}K).
 \begin{figure}[ht!]
         \centering
         \includegraphics[width=\linewidth]{Figures/simulation_model_comparison.pdf}
@@ -300,7 +300,7 @@ Variability in ion channel expression often correlates with the expression of ot
 The variability of ion currents and degeneracy of neurons may account, at least in part, for the observation that the effect of toxins within a neuronal type is frequently not constant \citep{khaliq_relative_2006, puopolo_roles_2007, ransdell_neurons_2013}.
 
 \subsection*{Effects of KCNA1 Mutations}
-Moderate changes in delayed rectifier potassium currents change the bifurcation structure of Hodgkin Huxley model, with changes analogous to those seen with \Kv mutations resulting in increased excitability due to reduced thresholds for repetitive firing \citep{hafez_altered_2020}. Although the Hodgkin Huxley delayed rectifier lacks inactivation, the increases in excitability seen are in line with both score-based and simulation-based predictions of the outcomes of \textit{KCNA1} mutations.  LOF KCNA1 mutations generally increase neuronal excitability, however the different effects of KCNA1 mutations across models on AUC are indicative that a certain cell type specific complexity exists. Increased excitability seen experimentally with \Kv null mice \citep{smart_deletion_1998, zhou_temperature-sensitive_1998}, with pharmacological \Kv block \citep{chi_manipulation_2007, morales-villagran_protection_1996}, by \cite{hafez_altered_2020} and with  simulation-based predictions of KCNA1 mutations. Contrary to these results,  \cite{zhao_common_2020} predicted \textit{in silico} that the depolarizing shifts seen as a result of KCNA1 mutations broaden action potentials and interfere negatively with high frequency action potential firing, however comparability of firing rates is lacking in this study.    
+Moderate changes in delayed rectifier potassium currents change the bifurcation structure of Hodgkin Huxley model, with changes analogous to those seen with \Kv mutations resulting in increased excitability due to reduced thresholds for repetitive firing \citep{hafez_altered_2020}. Although the Hodgkin Huxley delayed rectifier lacks inactivation, the increases in excitability seen are in line with \textcolor{red}{both score-based and} simulation-based predictions of the outcomes of \textit{KCNA1} mutations.  LOF KCNA1 mutations generally increase neuronal excitability, however the different effects of KCNA1 mutations across models on AUC are indicative that a certain cell type specific complexity exists. Increased excitability seen experimentally with \Kv null mice \citep{smart_deletion_1998, zhou_temperature-sensitive_1998}, with pharmacological \Kv block \citep{chi_manipulation_2007, morales-villagran_protection_1996}, by \citet{hafez_altered_2020} and with  simulation-based predictions of KCNA1 mutations. Contrary to these results,  \citet{zhao_common_2020} predicted \textit{in silico} that the depolarizing shifts seen as a result of KCNA1 mutations broaden action potentials and interfere negatively with high frequency action potential firing, however \textcolor{green}{they varied stimulus duration between different models and therefore} comparability of firing rates is lacking in this study.     
 Different current properties, such as the difference in \(\textrm{I}_\textrm{A}\) and \IKv in the Cb stellate and STN model families alter the impact of KCNA1 mutations on firing highlighting that knowledge of the biophysical properties of a current and its neuronal expression is vital for holistic understanding of the effects of a given ion channel mutation both at a single cell and network level.
 
 \subsection*{Loss or Gain of Function Characterizations Do Not Fully Capture Ion Channel Mutation Effects on Firing}