Figure 4.

A572D-SCN5A functional data in HEK293 cells. A: Whole-cell Na current (I_Na) from representative experiments for D572 with or without the common polymorphism R558. Activation of sodium channels was measured at different voltage steps −120 mV to +50 mV with a 10-mV step at holding potential of −140 mV. B: Late I_Na after leak subtraction was measured as the mean current between 600 and 700 ms elicited by depolarization from −140 mV to −20 mV. C: Summary data showing the ratio of late I_Na to peak I_Na as a percentage from several cells. D: Protocols used to address the kinetics of I_Na represented as inset in each plot. Data obtained from the activation protocol to establish peak I_Na were fitted to a Boltzmann equation to obtain the midpoint of activation. Inactivation was measured by a two-step protocol, with a holding potential of −140 mV and 1-second conditioning pulse from −150 to 0 mV with a 10-mV step and fitted to a Boltzmann equation to obtain the midpoint of inactivation. Recovery from inactivation was measured using a two-pulse protocol where a conditioning step of 1 second to 0 mV inactivated I_Na, followed by a test pulse to 0 mV after a different recovery period at a recovery potential of −140 mV. Data were normalized to peak and fitted to an exponential to obtain fast and slow time constants (τ_f and τ_s) and the proportion of the slow component (A_s) (Table 1). *P <0.5 vs A572/H558, D572/H558, A572/R558.