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The voltage-gated K(+) channel Kv1.5 was expressed in Chinese hamster ovary cells, and its interaction with fluvoxamine was studied using a whole-cell patch-clamp technique. Fluvoxamine reduced Kv1.5 whole-cell currents in a reversible, concentration-dependent manner, with an IC(50) value of 2.0 microM, and a Hill coefficient of 0.7. Fluvoxamine-induced inhibition of Kv1.5 caused a time-dependent blockade without modifying the kinetics of current activation. Fluvoxamine additionally inhibited Kv1.5 in a closed/resting or nonconducting state after deactivation. Inhibition increased steeply between -30 and 0 mV, corresponding to the voltage range for channel opening. Inhibition displayed an additional voltage dependence at voltages greater than 0 mV, consistent with an electrical distance of 0.16. Fluvoxamine slowed the deactivation time course and a tail crossover phenomenon was observed when the tail currents, recorded in the presence and absence of fluvoxamine, were superimposed. Inhibition of Kv1.5 by fluvoxamine was use-dependent. These results suggest that fluvoxamine strongly inhibits Kv1.5 currents and the inhibition of Kv1.5 by fluvoxamine is mixed channel-state dependent.

Inhibitory Action of Fluvoxamine on Kv1.5 Currents