Table 1.
Pharmacology of recombinantly expressed SK channels.
| Toxins | ||||
|---|---|---|---|---|
| Compound | IC50 | SK1 (KCa2.1)a | SK2 (KCa2.2) | SK3 (KCa2.3) |
| Apamin | nM | 0.70b [245], 1.3d [246], 2.9i [247], 3.2i [48, 50], 5.1k [247], 7.7i [248], 8c [249], 12.2l [248], >100m [18, 49] | 0.027 [245], 0.03 [50], 0.063 [18], 0.07 d [246], 0.083 [247], 0.095 [47], 0.14 [249], | 0.63 [70], 1d [246], 1.1 [249], 1.4 [33], 2 [49], 3h [250], 4 [245], 13.2e [77], 19.1 [77], |
| PO5 | nM | 25 [57] | ||
| Scyllatoxin (Leiurotoxin I) | nM | 80 [247], 325 [57] | 0.29 [247], 0.3 [251] | 1.1 [57], 8.3 [33] |
| Lei-Dab7f | nM | 6000 [57] | 5.5 [57] | 2500 [57] |
| Tamapin | nM | 42 [62] | 0.024 [62] | 1.7 [62] |
| Tsk | nM | 198 [57] | ||
| Organic blockers/inhibitors | ||||
| Compound | IC50 | SK1 (KCa2.1)a | SK2 (KCa2.2) | SK3 (KCa2.3) |
| Quaternary Bicuculline salts | µM | 1.4 [252], 15.9 [247] | 1.1 [252], 25 [247] | 6.6 [70] |
| Dequalinium | µM | 0.44 [247], 0.48 [248] | 0.16 [247], 0.35 [76] | 30e [77] |
| d-Tubocurarine | µM | 23.5 [248], 27 [247], 30.8 [50], 76.2 [18], 354 [49] | 2.4 [18], 5.4 [49], 17 [247] | 210e [77] |
| UCL 1684 | nM | 0.76 [247] | 0.28 [253], 0.36 [247] | 5.8 [33], 9.5 [253] |
| UCL 1848 | nM | 1.1 [248] | 0.11 [47], 0.12 [33], | 2.1 [33] |
| Calyculin A | nM | 240e [77] | ||
| Okadaic acid | nM | 506e [77] | ||
| Amitriptyline | µM | 54.8 [76] | 39 [70] | |
| Carbamazepine | µM | 14.5 [76] | ||
| Chlorpromazine | µM | 12.8 [76] | 0.6 [70], 33 e [77] | |
| Cyproheptadine | µM | 15.3 [76] | 9.2 [70] | |
| Desipramine | µM | 29e[77] | ||
| Fluoxetine | µM | 9e [78] | 7e [78] | 17 [78], 20e [78] |
| Fluphenazine | µM | 13e [77] | ||
| Imipramine | µM | 21.7 [76] | 44e [77] | |
| Nortriptyline | µM | 20e [77] | ||
| Promethazine | µM | 31e [77] | ||
| Tacrine | µM | 53.7 [76] | ||
| Trifluoperazine | µM | 7.6 [76] | 48e [77] | |
| Methyl-laudanosine | µM | 1.2 [254] | 0.8 [254] | 1.8 [254] |
| Methyl-noscapine | µM | 5.9 [254] | 5.6 [254] | 3.9 [254] |
| NS8593g | µM | 415 [75] | 598 [75] | 726 [75] |
| 4-Aminopyridine (4-AP) | µM | 512 [70] | ||
| Tetraethylammonium (TEA) | nM | 5.2 [50], 14.1 [255], 14.6 [49] | 2.8 [255] | 8.7 [255] |
| Enhancers | ||||
| Compound | EC50 | SK1 (KCa2.1)a | SK2 (KCa2.2) | SK3 (KCa2.3) |
| 1-EBIO | µM | 631 [193] | 453 [72], 654 [66], 866 [193], 996 [68] | 87 [7], 545h [250], 789 [193, 250], 1040 [74] |
| Dichloro-EBIO (DCEBIO) | µM | 27 [72] | 12 [7], 16 [74], 28 [250], >100h [250], | |
| NS309 | µM | 0.62 [72] | 0.12 [7], 0.30 [74], 0.46 [250], 1.20h [250], | |
| CyPPA | µM | >100 (inactive [74]) | 14 [74] | 5.6 [74] |
| Riluzole | µM | 43 [69] | ||
| Zoxazolamine | µM | 696 [68] | ||
| Chlorzoxazone | µM | 87 [67], 960 [68] | ||
| GW275919X | µM | 170[250], >100h[250] | ||
| CCI7950 | µM | 5h [250] | ||
Reported are IC50 values obtained from electrophysiological recordings, rubidium flux and functional fluorescence assays. Underlined values have been obtained from the human SK channel clones, all other values from the rat SK channel clones.
a Rat SK1(rSK1) subunits do not seem to form functional homomeric channels [46–48].However, chimeric channel subunits containing the transmembrane domain of rSK1, including the pore region, and intracellular N and C termini or solely C termini of rat SK2 (rSK2) or human SK1 (hSK1), form channels with an IC50 for apamin >100 nM and for d-tubocurarine >50 µM [48].
b Second component with IC50 of 196 nM.
c Up to 39% residual current.
d Rubidium flux measurements.
e Fluorescence assays.
f Lei-Dab7: unnatural amino acid diaminobutanotate replacing methionine in Leiurotoxin at position 7 [57].
g NS8593 is not a classical blocker, but an inhibitory gating modulator, the first of its kind, that reduces the apparent affinity of the SK channels for Ca2+ [75].
h Results obtained by planar array electrophysiology (population patch [250]).
i Channels expressed in HEK293 cells.
k Channels expressed in CHO cells.
l Channels expressed in COS-7 cells.
m Channels expressed in X. laevis oocytes.