NS1643 has no significant effect on Kv11.3 inactivation and recovery from inactivation.

<p>(A) Inactivation of Kv11.3 channels was investigated by a triple pulse protocol. Starting from a holding potential of −80 mV, the potential was stepped to +80 mV (P1) for 350 ms. A subsequent 8 ms P2 pulse to −100 mV was followed by variable 450 ms test pulses to potentials between +80 and −100 mV (P3), with 10 mV decrements (see pulse protocol). (Aa) Current traces obtained before and after application of 10 µM NS1643. (Ab) Time constants of inactivation obtained from monoexponential fits to the decay phase of the current traces. Data are means ± SEM of paired experiments (<i>n = 5</i>). (Ac) As a measure of voltage-dependent inactivation, the ratio of the steady-state (I_ss) to the instantaneous current amplitude (I_max) elicited with the variable P3 pulse was plotted against the P3 pulse potential and data obtained before and after application of 10 µM NS1643 (<i>n = 5</i>) were fitted with a Boltzmann function. I_max was measured directly after the capacitance transient (0.4–0.5 ms after the peak) and I_ss was determined as mean current level during the last 50 ms of the P3 pulse (see inset beneath the pulse diagram). Current ratios for potentials more negative than −30 mV were not considered due to increasing channel deactivation at these potentials. (B) The time course of recovery from inactivation was investigated with variable repolarizing test pulses starting from the fully activated state of the Kv11.3 channels. (Ba) Current traces recorded with the indicated pulse protocol from the same cell in the absence and in the presence of 10 µM NS1643. (Bb) Means of the time constants of recovery from inactivation (τ_recovery) as a function of the membrane potential (<i>n</i> = 6).