External Na⁺ is a competitive inhibitor of K⁺ conductance through Kir2.1. (A) Lineweaver–Burk plot of the open (polyamine-unblocked) Kir2.1 conductance (G) at various [K⁺]_out levels (50, 20, and 10 mM) in the presence and absence of 100 mM external Na⁺ (left: −100 mV; right: 0 mV). The relative G values are the chord conductances normalized to the value obtained at 150 mM [K⁺]_out (0 Na⁺) in each experiment at each V. Error bars represent SD. (B) Apparent K_m values for Kir2.1 conductance in the presence and absence of 100 mM Na⁺ obtained from the slopes of the Lineweaver–Burk plots (left) and K_i values for Na⁺ inhibition (right). Lines show K_{m (without Na)}(V) = 2.2 ⋅ exp(V/601) and K_i(Na)(V) = 51 ⋅ exp(V/115). (C) Simulation of the inhibitory effects of external Na⁺ on polyamine-unblocked Kir2.1 conductance. G/G_max(V) values at different external conditions were calculated using G(V) = {G_max(V) ⋅ [K⁺]_out}/{K_{m (without Na)} ⋅ (1 + [Na⁺]_out/K_i(Na)) + [K⁺]_out}. See Materials and methods for the details of the analysis.