Modulation of the voltage-gated potassium channel Kv2.1 by the anti-tumor alkylphospholipid perifosine

Abstract

Background: The aim of the present study was to assess the effects of perifosine-a third generation alkylphospholipid analog with anti-tumor properties-on the activity of Kv2.1 channels.

Methods: The whole-cell patch clamp technique was applied to follow the modulatory effect of perifosine on Kv2.1 channels expressed in HEK293 cells.

Results: Obtained data provide evidence that perifosine application decreases the whole cell Kv2.1 currents in a concentration-independent manner. Perifosine induces a hyperpolarizing shift in the voltage dependence of Kv2.1 channels inactivation without altering the voltage dependence of channels activation. The kinetics of Kv2.1 closed-state inactivation was accelerated by perifosine, with no significant effects on the recovery rate from inactivation.

Conclusions: Taken together, these results show that perifosine modified the Kv2.1 inactivation gating resulting in a decrease of the current amplitude. These data will help to elucidate the mechanism of action of this promising anti-cancer drug on ion channels and their possible implications.

Keywords: Alkylphospholipid; Kv2.1; Perifosine; Potassium channels.