Figure 3. The gating pore current increases the susceptibility to paradoxical depolarization in low extracellular [K⁺].

The steady-state I–V relation for mammalian skeletal muscle was simulated by the combination of an inward rectifier K⁺ current, I_Kir, a delayed rectifier K⁺ current, I_KDR, and a leakage current with a reversal potential of 0 mV, I_Leak, as in Struyk & Cannon (2008). A, in 4 mm[K⁺]_o the resting potential of −91.3 mV is determined primarily from the balance of an inward I_Leak and outward I_Kir. Addition of a gating pore current, I_gp, to simulate HypoPP (dashed red line), shifts the I–V relation downward (dashed black line) but results in only a small depolarization of V_rest to −87.3 mV. B, reduction of [K⁺]_o to 2.5 mm shifts E_K and I_Kir to more negative potentials, with a predicted hyperpolarization of V_rest to −101.6 mV in WT fibres. For HypoPP fibres, however, V_rest depolarizes to −65.3 mV (arrow) because the combination of inward currents (I_Leak+I_gp) exceeds the outward current from I_Kir. Under these conditions, which would result in paralysis from inactivation of sodium channels, V_rest is now set by the balance of I_KDR and the inward currents. Because K_DR channels are active only for >−55 mV, V_rest is strongly dependent on K_DR gating, which results in an apparent decoupling of V_rest from E_K. C, phase plot of V_rest as a function of [K⁺]_o for simulated WT and HypoPP fibres. The inward gating pore current in HypoPP fibres causes only a small depolarization of V_rest from −91.3 mV to −87.3 mV in 4 mm[K⁺]_o (arrow). More importantly, the catastrophic depolarization of V_rest shifts leftward from 1.5 mm[K⁺]_o for WT to 3 mm for HypoPP. The Nernst potential for K⁺, E_K, is shown for comparison (blue line).