Gating modulation and potentiation of amiodarone blockage of the Kv10.1 potassium channel bu KB130015, an amiodarone derived molecule.

Kv10.1 is a voltage-gated K+ channel whose structure-function relationships remain incompletely understood, and whose ectopic expression is linked to tumorigenesis. We have recently shown that the antiarrhythmic drug amiodarone inhibits both the K+ current and the characteristic Cole-Moore shift of Kv10.1. Here, we examined whether the amiodarone derivative KB130015 similarly modulates Kv10.1 function. Low micromolar concentrations of KB130015 markedly accelerated current activation across all tested holding potentials and fully abolished the Cole-Moore shift. The t1⁄2 reduction induced by KB130015 was voltage independent. KB130015 also slowed channel deactivation to a similar extent at all voltages and shifted the G-V relationship toward more negative potentials without altering its slope. Despite these pronounced gating effects, current amplitude increased only slightly and showed minimal dependence on KB130015 concentration. Notably, KB130015 enhanced the inhibitory effect of amiodarone on K+ current. These results identify KB130015 as a potent modulator of Kv10.1 gating that also potentiates amiodarone-mediated inhibition.