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Gating Modulation of the Tumor-Related Kv10.1 Channel by Mibefradil.
Journal of Cellular Physiology 2017 August
Several reports credit mibefradil with tumor suppressing properties arising from its known inhibition of Ca(2+) currents. Given that mibefradil (Mb) is also known to inhibit K(+) channels, we decided to study the interaction between this organic compound and the tumor-related Kv10.1 channel. Here we report that Mb modulates the gating of Kv10.1. Mb induces an apparent inactivation from both open and early closed states where the channels dwell at hyperpolarized potentials. Additionally, Mb accelerates the kinetics of current activation, in a manner that depends on initial conditions. Our observations suggest that Mb binds to the voltage sensor domain of Kv10.1 channels, thereby modifying the gating of the channels in a way that in some, but not all, aspects opposes to the gating effects exerted by divalent cations. J. Cell. Physiol. 232: 2019-2032, 2017. © 2016 Wiley Periodicals, Inc.
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