Effect of psoralen on the cloned Kv3.1 currents

Abstract

The psoralen, a furocoumarin derivative, on the cloned neuronal rat Kv3.1 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Psoralen reduced Kv3.1 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 2.3 +/- 0.03 microM and 0.9 +/- 0.08, respectively. Psoralen accelerated the decay rate of inactivation of Kv3.1 currents without modifying the kinetics of current activation. The psoralen-induced inhibition of Kv3.1 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Psoralen slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of psoralen, were superimposed. Inhibition of Kv3.1 by psoralen was use-dependent at a frequency of 1 Hz. The present results suggest that psoralen acts on Kv3.1 currents as an open-channel blocker.

Open channel block of Kv1.5 currents by citalopram

“…This can be explained if the dissociation rate of citalopram is lower than the transition rate between the open and the closed (or resting) state under control conditions. This tail crossover phenomenon suggests an interaction between citalopram and the open state of Kv1.5 as previously reported [21,26,27] . 4) The actions of citalopram in inhibiting Kv1.5 were usedependent, with effects enhanced at higher rates of channel activation.…”

“…The voltage-dependent inhibition of Kv1.5 by citalopram implies that the inhibition of Kv1.5 by citalopram occurs preferentially after the channels are open [21,25,26] . 3) Citalopram slowed the deactivation time course, resulting in a tail crossover phenomenon.…”

“…4) The actions of citalopram in inhibiting Kv1.5 were usedependent, with effects enhanced at higher rates of channel activation. One of the features of open channel blockers is a use-dependent inhibition because the blockers would have a higher chance to bind to channel pores as the channels open more frequent ly [21,25,26,28] . This is consistent with the actions of citalopram on the open state of Kv1.5.…”

Blockade of Kv1.5 channels by the antidepressant drug sertraline

“…3) The inhibition of Kv1.5 induced by sertraline was highly voltage-dependent and increased steeply in the voltage range of channel activation. The voltage-dependent inhibition of Kv1.5 by sertraline implies that the inhibition of Kv1.5 by sertraline occurs preferentially after the channels are open [ 15 19 20 21 22 23 24 ]. 4) Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon.…”

“…5) The actions of sertraline in inhibiting Kv1.5 were use-dependent, with effects enhanced at higher rates of channel activation. One of the features of open channel blockers is a use-dependent inhibition because the blockers would have a higher chance to bind to channel pores as the channels open more frequently[ 15 19 20 21 24 26 ]. This is consistent with the actions of sertraline on the open state of Kv1.5.…”