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

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      Publication Details (including relevant citation   information):

        LIPID RAFTSCANCER   CELLSK+   CHANNELSEXPRESSIONPROLIFERATIONINHIBITIONEDELFOSINERESISTANCEMOLECULESAPOPTOSIS

      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.

      Address (URL): http://www.sciencedirect.com/science/article/pii/S1734114015003540