We next assessed the functional parameters of derived human DA neurons from subjects with D398 or N398 variants. Using whole cell patch clamp recordings, we found that both the D398 and N398 DA cultures produced robust and repetitive spontaneous action potentials (APs) (Fig. 2A,B) and had similar membrane properties, including membrane capacitance, resting membrane potentials, and input resistance (Fig. 2C–E). While the spontaneous APs in DA neurons of both genotypes have statistically similar frequencies (p = 0.258), the N398 neurons tend to fire more APs (Fig. 2F). Next, we tested the intrinsic excitability of these DA neurons by inducing APs using different amplitudes of current injections; however, neurons of both genotypes exhibited similar neuronal excitability as indicated by a similar frequency of induced APs (Fig. 2G,H). These data suggest that the N398 variant in CHRNA5 does not impair neuronal excitability, nor does it produce any major changes in the passive membrane properties of D398 and N398 human neurons (Fig. 2I). However, while DA neurons with different CHRNA5 gene variants have similar intrinsic excitabilities, the N398 variants also have a slightly
