SKF 96365 hydrochloride

SKF 96365 hydrochloride is a synthetic blocker of Ca_V3 (T-type) voltage gated calcium channels and of TRPC channels. In addition, it has a blocking effect on potassium channels. SKF also inhibits the calcium sensor STIM1 which enables Store-operated Ca²⁺ entry (SOCE). SKF has an effective concentration of 1-100 µM and an IC₅₀ of 560 nM for Ca_V3.1 channel. SKF is used to identify Ca_V3 and TRPC channels in many cell types. In an experiment examining the effect of SKF on Ca_V3 conductivity, perfusion of 1 µM of SKF reversibly inhibited 86.3±0.1% of Ca_V3.1 currents generated in HEK293 cells. Maximum inhibition was reached within 6-7 minutes. Application of larger concentrations of SKF completely abolished Ca_V3.1 channel currents. SKF blocks the Ca_V3.1 channel in a tonic manner indicating it interacts with the channel regardless of its functional state, unlike other Ca_V channel blockers. In the same experiment SKF also abolished calcium currents in other types of Ca_V channels such as P/Q-type and N-type.

Blockade of these channels was only partially reversible due to possible irreversible binding of or longer washing time required. In addition, SKF blocks L-type calcium channels but in a much slower manner than other calcium channels.