Inhibitory effects of antidepressant fluoxetine on cloned Kv2.1 potassium channel expressed in HEK293 cells

It is well demonstrated that antidepressant fluoxetine has significant inhibitory effects on voltage-gated potassium channels. So far, the concise regulation of fluoxetine on Kv2.1, the predominant delayed rectifier potassium channel subtype in the central nervous system, are rarely reported. Here patch-clamp recording was used to investigate the inhibitory effects of fluoxetine on Kv2.1 potassium channels stably expressed in HEK293 cells. The results showed fluoxetine dose-dependently suppressed Kv2.1 currents with an IC₅₀ of 51.3 μM. At the test potential positive to +50 mV, fluoxetine 50 μM voltage-dependently suppressed Kv2.1 currents with an electrical distance δ of 0.28. Moreover, fluoxetine 50 μM did not affect the activation process of Kv2.1, but reduced the decay time constant τ_inact and obviously accelerated the inactivation process of Kv2.1 and left-shifted the half-maximal inactivation potential of Kv2.1 potassium channel by 9.8 mV. Fluoxetine 50 μM notably delayed the recovery process of Kv2.1 from inactivation with increased time constants. In addition, fluoxetine 50 μM use-dependently inhibited Kv2.1 currents at different frequencies. In conclusion, the inhibition of Kv2.1 by fluoxetine was concentration-dependent, voltage-dependent and use-dependent. The accelerated steady-state inactivation of Kv2.1 channels induced by fluoxetine might be ascribed to the delay of the recovery process of Kv2.1.