Figure 7.

Proposed model to explain how edelfosine decreases SK3/K_Ca2.3-dependent cancer cells migration. When SK3/K_Ca2.3 channels are expressed and active in plasma membranes, they hyperpolarize the membrane. This leads to an increase of Ca²⁺ entry through voltage-independent Ca²⁺ channels and raised [Ca₂₊]_i, promoting cell migration. This model proposes that edelfosine incorporates within plasma membrane and blocks SK3/K_Ca2.3 channel-induced hyperpolarization. This leads to a membrane depolarization and to a decrease of the driving force for Ca²⁺ and then to decreased SK3/K_Ca2.3 channel activity. Additionally, edelfosine reduced the Ca²⁺ sensitivity of SK3/K_Ca2.3 channels, leading to a further reduction of SK3/K_Ca2.3 channel activity. Consequently, [Ca₂₊]_i is reduced and cell migration decreased. The inset represents the cone shape form proposed for edelfosine [modified from (Patel et al., 2001)].