Key result
Fluticasone propionate potentiates Kv1 channel current with a half-maximum effective concentration of 37 ± 1.1 nM, demonstrating greater efficiency than cortisone.
Fluticasone propionate is a highly potent potentiator of Kv1 channels, providing a basis for designing small-molecule compounds to modulate Kv1-Kvβ complexes.
Potent Kv1 potentiation offers a scaffold for modulator design; leaves open translation to cardiovascular disease models.
The Kv1 family voltage-dependent K(+) channels are essential for termination of action potentials in neurons and myocytes. These channels form a stable complex with their beta subunits (Kvβ), some of which inhibit channel activity. Cortisone potentiates Kv1 channel by binding to Kvβ and promoting its dissociation from the channel, but its half-maximum effective concentration is ∼46 μM. To identify corticosteroids that are more efficient than cortisone, we examined 25 cortisone analogues and found that fluticasone propionate potentiates channel current with a half-maximum effective concentration (EC(50)) of 37 ± 1.1 nM. Further studies showed that fluticasone propionate potentiates channel current by inducing dissociation of Kvβ, and docking of fluticasone propionate into the cortisone binding site reveals potential interactions that enhance the EC(50) value. Thus, fluticasone propionate provides a starting point for rational design of more efficient small-molecule compounds that increase Kv1 activity and affect the integrity of the Kv1-Kvβ complex.
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Pan et al. (2012) studied this question. Fluticasone propionate vs. Cortisone was evaluated on Half-maximum effective concentration (EC50) for potentiating channel current. Fluticasone propionate potentiates Kv1 channel current with a half-maximum effective concentration of 37 ± 1.1 nM, demonstrating greater efficiency than cortisone.
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