Figure 1. Effect of Na⁺_o on HERG recovery from inactivation in the absence of K⁺_o.

Membrane potential was stepped from −80 mV to +50 mV (2 s), followed by test potentials of −50 or −100 mV. A and B, representative currents at hyperpolarized test potentials for a paired experiment in which [Na⁺]_o was changed from 0 (A) to 146 mm (B), with [K⁺]_o held at 0. The currents in 146 mm Na⁺_o were much smaller than those in 0 Na⁺_o (note current scale is different while time scale is identical). Experiments as in A and B were carried out with several concentrations of Na⁺_o. The early, increasing phase reflecting recovery from inactivation (ending at the point indicated by arrows) was fitted with a single exponential. Time constants at several [Na⁺]_o are plotted in C (n = 4–5, paired observations). For test potentials of both −50 mV and −100 mV, recovery time constants were significantly smaller than baseline ([Na⁺]_o= 0) for [Na⁺]_o≥ 40 mm (P < 0.05). D, Na⁺_o concentration–response relationship in the absence of K⁺_o for peak tail current at −50 mV. Normalized peak tail current (I_Na/I_0Na) is plotted on the y-axis. Note that the IC₅₀ of 4.2 ± 1.2 mm is similar to that previously measured at +20 mV (Numaguchi et al. 2000a; Mullins et al. 2002) (see also Fig. 2A and inset).