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Vol. 291, Issue 1, 1-6, October 1999
Department of Physiology, College of Medicine, The Catholic
University of Korea, Socho-gu, Seoul, Korea
The effects of fluoxetine (Prozac), a widely used antidepressant drug,
on Kv1.3 stably expressed in Chinese hamster ovary cells were examined
using the whole-cell and excised inside-out configurations of the
patch-clamp technique. In whole-cell recordings, fluoxetine accelerated
the decay rate of inactivation of Kv1.3 and thus decreased the current
amplitude at the end of the pulse in a concentration-dependent manner
with an IC50 value of 5.9 µM. The inhibition displayed a
weak voltage dependence, increasing at more positive potentials.
Neither the activation nor the steady-state inactivation curve was
affected by fluoxetine. In addition, fluoxetine reduced the tail
current amplitude and slowed the deactivation of the tail current,
resulting in a crossover phenomenon. When applied to the internal side
of the membrane in inside-out recordings, the inhibition by fluoxetine
was much faster and more potent with an IC50 value of 1.7 µM compared with whole-cell recordings. Norfluoxetine, the major
metabolite of fluoxetine, also inhibited Kv1.3 in a concentration-dependent manner (IC50 = 1.4 µM) in
whole-cell recordings. To check whether the fluoxetine-induced
inhibition demonstrated in cloned Kv1.3 could also be observed in
native T lymphocytes, the effects of fluoxetine were investigated on
human T lymphocytes. Fluoxetine also inhibited outward K+
current in human T lymphocytes. Our results indicate that fluoxetine produced a concentration- and voltage-dependent inhibition of Kv1.3
that can be interpreted as an open channel block and that a binding
site for fluoxetine is more accessible from the intracellular side.
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