Objectives: The mechanisms of selective motoneuron (MN) degeneration in amyotrophic lateral sclerosis (ALS) are still unresolved. Electrophysiological studies on transgenic (tg) SOD1G93A ALS mice identified increased TTX-sensitive persistent sodium currents e.g. in presymptomatic early postnatal (<=10 days) MNs. Accordingly, enhanced persistent sodium channel activity was proposed as a candidate mechanism for an overexcitability-mediated MN death in ALS. However, it was unknown whether changes of persistent sodium channel activity were still present during the relevant time window between 3 and 4 months of age, when the progressive degeneration of vulnerable MN populations in SOD1G93A mice leads to ALS-like motor symptoms and finally death. Methods: To address this issue, we developed a brainstem slice preparation to perform whole-cell patch clamp recordings on adult vulnerable hypoglossal MNs during disease progression and endstage. Results: Investigating electrophysiological parameters of tg MNs in late disease stages (4 months) and age- matched wildtype controls (wt), we observed no differences in the properties of persistent TTX-sensitive sodium currents. We also found no significant differences in the f-I gain or current threshold for the initial spike between tg and control MNs in this age group. Conclusion: While the persistent sodium current densities of adult wt and tg MNs were similar to those reported for young wt mice (van Zundert et al. 2008. J Neurosci 28(43), 10864-10874), other electrophysiological properties dramatically changed with the maturation of MNs (e.g. f-I gain was reduced to the half). Our data indicate that changes in persistent sodium currents and parameters of cellular excitability identified in MNs from presymptomatic ALS mice are not present during the active phase of degeneration. Thus, it appears to be rather unlikely that persistent sodium currents play an active degeneration-promoting role in the SOD1G93A mouse model of ALS.