Pharmacological characterization of small‐conductance Ca2+‐activated K+ channels stably expressed in HEK 293 cells

Three genes encode the small‐conductance Ca2+‐activated K+ channels (SK channels). We have stably expressed hSK1 and rSK2 in HEK 293 cells and addressed the pharmacology of these subtypes using whole‐cell patch clamp recordings. The bee venom peptide apamin blocked hSK1 as well as rSK2 with IC50 values of 3.3 nM and 83 pM, respectively. The pharmacological separation between the subtypes was even more prominent when applying the scorpion peptide blocker scyllatoxin, which blocked hSK1 with an IC50 value of 80 nM and rSK2 at 287 pM. The potent small molecule blockers showed little differentiation between the channel subtypes. The bis‐quinolinium cyclophane UCL 1684 blocked hSK1 with an IC50 value of 762 pM and rSK2 at 364 pM. The antiseptic compound dequalinium chloride blocked hSK1 and rSK2 with IC50 values of 444 nM and 162 nM, respectively. The nicotinic acetylcholine receptor antagonist d‐tubocurarine was found to block hSK1 and rSK2 with IC50 values of 27 μM and 17 μM when measured at +80 mV. The inhibition by d‐tubocurarine was voltage‐dependent with increasing affinities at more hyperpolarized potentials. The GABAA receptor antagonist bicuculline methiodide also blocked hSK1 and rSK2 in a voltage‐dependent manner with IC50 values of 15 and 25 μM when measured at +80 mV. In conclusion, the pharmacological separation between SK channel subtypes expressed in mammalian cells is too small to support the notion that the apamin‐insensitive afterhyperpolarization of neurones is mediated by hSK1. British Journal of Pharmacology (2000) 129, 991–999; doi:10.1038/sj.bjp.0703120