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To understand the basis of clinical heterogeneity in SCN2A -associated disorders, the biophysical consequences of Na v 1.2 channel mutations and their impact on action potential firing and neuronal excitability must be clarified. Representative current traces from Chinese hamster ovary (CHO) cells transiently expressing wild-type or mutant Na v 1.2 channels are shown in Fig. 1 B . Peak sodium current ( I Na ) densities in cells expressing L1563V channels were similar to those of wild-type channels, whereas I Na densities were decreased in cells harboring R853Q channels and increased in cells harboring R1882Q channels (Fig. 1 C and Table 2). The effects of mutations on Na v 1.2 channel gating over a range of membrane potential ( V m ) values are shown in Fig. 1 D . Relative to wild-type, the activation curves of R853Q and L1563V channels exhibited small but statistically significant hyperpolarizing or depolarizing shifts, respectively. R1882Q channel activation was more severely affected, resulting in a 6-mV hyperpolarizing shift of the V 0.5,act value, a change that results in increased sodium-channel availability compared with the wild-type (Fig. 1 D and Table 2). In all mutants, the V 0.5,inact values were significantly changed compared with wild-type (Fig. 1 D and Table 2). In cells expressing R853Q channels, the hyperpolarizing shift of V 0.5,inact stabilizes inactivation and leads to reduced sodium-channel availability at physiologically relevant V m values. Conversely, the depolarizing shift of V 0.5,inact increases sodium-channel availability for L1563V and R1882Q variants. Venomous villain mf doom born Soluto svizzero tedesco racing Venomous villain mf doom born Venomous villain mf doom born Venomous villain mf doom born Venomous villain mf doom born * This phone number available for 3 min is not the recipient's number but a number from a service which will put you through to that person. This service is produced by Kompass. Why this number ? NEW PROLINE TIRES for rc trucks (lv)
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