Co²⁺, Zn²⁺, and La³⁺ cause a positive shift in the voltage dependence of Q_OFF-V relationships for hERG1, but they do not induce a transient outward component in Ig_OFF. (A) Q_OFF-V relationships for hERG1 measured under control conditions ([Ca²⁺]_e = 2 mM) and after the addition of 3 mM Co²⁺ (n = 3). Control: V_1/2 = −15.9 ± 0.8 mV and z = 2.20 ± 0.08; Co²⁺: V_1/2 = 19.1 ± 0.9 mV and z = 1.34 ± 0.02. (B) Ig traces recorded in the presence of 2 mM Ca²⁺ (control) and 3 mM Co²⁺ at a test potential of +60 mV. Ig_OFF was measured at −110 mV. (C) Ig_OFF traces from B are shown at expanded time (initial 5 ms) and amplitude scales. (D) Q_OFF-V relationships for hERG1 measured under control conditions ([Ca²⁺]_e = 2 mM) and after the addition of 1 mM Zn²⁺ (n = 3). Control: V_1/2 = −17.5 ± 0.3 mV and z = 1.82 ± 0.03; Zn²⁺: V_1/2 = 16.4 ± 6.3 mV and z = 0.97 ± 0.06. (E) Ig traces recorded in the presence of 2 mM Ca²⁺ (control) and 1 mM Zn²⁺ at a test potential of +60 mV. Ig_OFF was measured at −110 mV. (F) Ig_OFF traces from E are shown at expanded time (initial 5 ms) and amplitude scales. (G) Q_OFF-V relationships for hERG1 measured under control conditions ([Ca²⁺]_e = 2 mM) and after the addition of 10 µM La³⁺ (n = 3). Control: V_1/2 = −20.6 ± 0.4 mV and z = 2.18 ± 0.06; La³⁺: V_1/2 = 19.3 ± 3.9 mV and z = 1.23 ± 0.08. (H) Ig traces recorded in the presence of 2 mM Ca²⁺ (control) and 10 µM La³⁺ at a test potential of +60 mV. Ig_OFF was measured at −110 mV. (I) Ig_OFF traces from H are shown at expanded time (initial 5 ms) and amplitude scales.