Table A1.
Inhibitory effects of spider knottins on NaV channel subtypes. Values presented were obtained from electrophysiological experiments unless otherwise as stated.
| Toxin | NaSpTx Family | NaV1.1 | NaV1.2 | NaV1.3 | NaV1.4 | NaV1.5 | NaV1.6 | NaV1.7 | NaV1.8 | NaV1.9 | Others |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ProTx-I | 2 | 51 nM (n, X, h); 72 nM (s, X, h); [103] |
27 nM (n, X, r) [103] |
||||||||
| ProTx-II | 3 | 15.8 nM (s, C, h) [141] | 52.9 nM (n, H, rNav1.2a) [104] 41 nM (n, H, h) [132] 79.4 nM (s, H, h) [141] |
109.9 nM (n, H, r) [104] 102 nM (n, C, h) [132] 25 nM (s, h) [141] |
107.6 nM (n, H, r) [104] 39 nM (n, H, h) [132] 79.4 nM (s, H, h) [141] |
29 nM (s, H, h) [103] 79.4 nM (n, H, h) [104] 79 nM (n, H, h) [132] 398 nM (s, H, h) [141] |
26 nM (n, H, h) [132] 31.6 nM (s, C, h) [141] |
0.7 nM (n, H, h) [104] 0.3 nM (n, H, h) [132] 0.8 nM (s, H, h) [141] |
19 nM (n, X, r) [103] 146 nM (n, H, h) [132] |
||
| GP-W7Q-W30L ProTx-II | 3 | 6310 nM (s, C, h) [141] | 794 nM (s, H, h) [141] |
15,849 nM (s, H, h) [141] | >3162 nM (s, H, h) [141] | 2512 nM (s, C, h) [141] |
10 nM (s, H, h) [141] | ||||
| ProTx-III | 1 | 60 nM, rec-G; 101 nM, s-OH; 11.3 nM, s-NH2
(H, h) [80] |
21.9 nM, rec-G; 41.3 nM, s-OH; 11.5 nM, s-NH2 (H, h) [80] | >500 nM, rec-G and s-OH; >50 nM, s-NH2 (H, h) [80] | 9.5 nM, rec-G; 11.5 nM, s-OH; 2.5 nM, s-NH2 (H, h) [80] | ||||||
| HwTX-IV | 1 | 41 nM (n, H, h) [237] | 150 nM (n, H, r) [114] 10 nM, s-NH2, 54 nM, rec (H, h) [83] 44 nM (n, H, h) [237] |
338 nM (n, H, r) [114] 190 nM (n, H, h) [237] |
400 nM (n, H, r) [114] >10,000 nM (n, H, h) [237] |
>10,000 nM (n, H, h) [114] >10,000 nM (n, H, h) [237] |
52 nM (n, H, h) [237] 83.3 nM (n, H, h) [237] |
22.7 nM (n, H, h) [104] 26 nM (n, H, r) [114] 16 nM, s-NH2, 55 nM, rec (H, h) [83] 17 nM (s, H, h) [142] 32.4 nM (s, S, h, FLIPR) [137] 100 nM (n, H, h) [237] 32.6 nM (n, H, h, Manual ephys) [237] |
>10,000 nM (n, H, h) [237] | 30 nM (n, TTX-S currents, rat DRG) [113] | |
| E1G-E4G-Y33W HwTx-IV | 1 | 8.4 nM (rec, H, h) [143] 1100 nM (rec, H, h, FLIPR) [143] |
11.9 nM (rec, H, h) [143] 540 nM (rec, H, h, FLIPR) [143] |
7.2 nM (rec, H, h) [143] 1400 nM (rec, H, h, FLIPR) [143] |
369 nM (rec, H, h) [143] >30,000 nM (rec, H, h, FLIPR) [143] |
Insensitive up to 1000 nM (rec, H, h) [143] >30,000 nM (rec, H, h, FLIPR) [143] |
6.8 nM (rec, C, h) [143] 600 nM (rec, H, h, FLIPR) [143] |
0.4 nM (s, H, h) [142] 3.3 nM (rec, C, h) [143] 5100 nM (rec, H, h, FLIPR) [143] |
Insensitive up to 1000 nM (rec, C, h) [143] >30,000 nM (rec, H, h, FLIPR) [143] |
||
| E1G-E4G-F6W-Y33W HwTx-IV | 1 | 7.55 nM (s, S, h, FLIPR) [137] | |||||||||
| HnTx-I | 1 | 68,000 nM (n, X, r) [145] | >10,000 nM (s, H, h) [238] |
No inhibition of TTX-S and TTX-R currents up to 100,000 nM [145] | |||||||
| G7W-N24S HnTx-I | 1 | 440 nM (rec, C, h) [81] | |||||||||
| E1G-N23S-D26H-L32W HnTx-I | 1 | 3.6 nM (s, H, h) [238] | |||||||||
| HnTx-III | 1 | 1270 nM (n, H, h) [117] | 275 nM (n, H, h) [117] |
491 nM (n, H, h) [117] |
No activity [117] | No activity [117] | 232 nM (n, H, h) [117] | 1.1 nM (TTX-S rat DRG); No inhibition in TTX-R currents [116] | |||
| HnTx-IV | 1 | 36.1 nM (n, H, r) [129] |
375 nM (n, H, r) [129] |
>10,000 nM (n, H, r) [129] | No inhibition up to 1000 nM [129] | 21 nM (s, n, H, h) [127] | 44.6 nM (TTX-S rat DRG) [116] 34 nm (TTX-S rat DRG) [85] |
||||
| JzTx-III | 7 | No effect [106] | No effect [106] | No effect [106] | 348 nM (rec, H, h) [106] | No effect [106] | No effect [106] | 380 nM (n, rat cardiac myocytes) [105] | |||
| JzTx-V | 3 | 292 nM (s, H, h) [79] |
5.12 nM (s, H, r) [79] |
2700 nM (s, H, h) [79] |
61 nM (s, H, h) [79] | 27.6 nM (n, TTX-R currents, rat DRG); 30.2 nM (n, TTX-S currents, rat DRG) [107] | |||||
| JzTx-IX | 2 | 5420 nM (n, HT) [108] |
450 nM (n, HT) [108] |
650 nM (n, TTX-R currents, rat DRG); 360 nM (n, TTX-S currents, rat DRG) [108] | |||||||
| JzTx-XI | 2 | 124 nM (n, C) [91] |
|||||||||
| JzTx-14 | 3 | 194 nM (n, HT, M) [125] |
426.3 nM (n, HT, M) [125] | 290.1 nM (n, HT, M) [125] | 478 nM (n, HT, M) [125] |
158.6 nM (n, HT, M) [125] |
188.9 nM (n, HT, M) [125] | 824 nM (n, HT, M) [125] |
|||
| JzTx-34 | 2 | No inhibition (s, HT, r) [119] | No inhibition (s, HT, r) [119] | 7950 nM (s, HT, r) [119] |
No inhibition (s, HT, r) [119] | No inhibition (s, HT, r) [119] | No inhibition (s, HT) [119] | 610 nM (s, HT, h) [119] | No inhibition (s, ND cells, h) [119] | 85 nM (rec, TTX-S currents, rat DRG); No inhibition in TTX-R currents [118] 91 nM (s, TTX-S currents, rat DRG); No inhibition in TTX-R currents [119] |
|
| JzTx-35 | 2 | 1070 nM (n, H, h) [112] | |||||||||
| CcoTx-1 | 1 | 523 nM (n, X) [73] 1060 nM (n, H, h, FLIPR) [110] |
3 nM (n, X) [73] 70 nM (n, H, h, FLIPR) [110] |
No activity [73] >10,000 nM (n, H, h, FLIPR) [110] |
888 nM (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
323 nM (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
>10,000 nM (n, H, h, FLIPR) [110] | 5120 nM (n, H, h, FLIPR) [110] | 55% block (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
||
| CcoTx-2 | 1 | 407 nM (n, X) [73] 170 nM (n, H, h, FLIPR) [110] |
8 nM (n, X) [73] 80 nM (n, H, h, FLIPR) [110] |
88 nM (n, X) [73] 5570 nM (n, H, h, FLIPR) [110] |
400 nM (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
1634 nM (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
3990 nM (n, H, h, FLIPR) [110] | 230 nM (n, H, h, FLIPR) [110] | 40% block (n, X) [73] >10,000 nM (n, H, h, FLIPR) [110] |
||
| CcoTx-3 | 2 | No activity [73] | No activity [73] | No activity [73] | No activity [73] | 447 nM (n, X) [73] | 45% block (n, X) [73] | ||||
| PaurTx3 | 1 | 610 nM (n, X) [73] |
0.6 nM (n, X) [73] |
42 nM (n, X) [73] |
288 nM (n, X) [73] |
72 nM (n, X) [73] |
65% block (n, X) [73] | ||||
| Hm-1 | 9 | 32.4% block at 200 nM (n, X, r) [120] | 336.4 nM (n, X, r) [120] 40% block at 200 nM (n, X, r) [120] |
36.5% block at 200 nM (n, X, h) [120] | 38.7% block at 200 nM (n, X, m) [120] |
||||||
| Hm-2 | 9 | 64.6% block at 200 nM (n, X, r) [120] | 154.8 nM (n, X, r) [120] 61.9% block at 200 nM (n, X, r) [120] |
17.8% block at 200 nM (n, X, h) [120] | 38.7% block at 200 nM (n, X, m) [120] |
||||||
| GTx1-15 | 1 | 120 nM (s, H, h) [239] |
No effect up to 2000 nM (s, H, h) [239] | 7 nM (s, H, h) [239] |
No effect up to 930 nM (s, H, h) [239] | ||||||
| VSTx-3 | 1 | 190 nM (s, H, h) [239] | No effect up to 1000 nM (s, H, h) [239] | 430 nM (s, H, h) [239] | 770 nM (s, H, h) [239] | ||||||
| Hd1a | 1 | 87% block (rec, X, h) [121] | 55% block (rec, X, h) [121] | 23%–31% block (rec, X, h) [121] |
23%–31% block (rec, X, h) [121] |
No inhibition up to 1000 nM (rec, X, h) [121] |
23%–31% block (rec, X, h) [121] |
111 nM (rec, X, h) [121] 87% block (rec, X, h) [121] |
No inhibition up to 1000 nM (rec, X, h) [121] |
||
| Cd1a | 1 | 2180 μM (s, H, h, FLIPR) [110] | 130 μM (s, H, h, FLIPR) [110] | >30,000 nM (s, H, h, FLIPR) [110] | >30,000 nM (s, H, h, FLIPR) [110] | >30,000 nM (s, H, h, FLIPR) [110] | >30,000 nM (s, H, h, FLIPR) [110] | 3340 nM (s, H, h, FLIPR) [110] 16 nM (s, H, h) [110] |
6920 nM (s, H, h, FLIPR) [110] |
||
| Pre1a | 1 | 57.1 nM (s, H, h) [111] | 189.6 nM (s, X, r) [111] | 8000 nM (s, X, r) [111] |
16.5% block at 1000 nM (s, X, r) [111] | 8.6% block at 1000 nM (s, X, r) [111] | 221.6 nM (s, H, h) [111] |
114 nM (s, X, r) [111] 15 nM (s, H, h) [111] |
|||
| Pn3a | 2 | 37 nM (s, H, h) [61] |
124 nM (s, H, h) [61] |
210 nM (s, H, h) [61] ( |
144 nM (s, H, h) [61] |
800 nM (s, H, h) [61] |
129 nM (s, H, h) [61]) |
0.9 nM (s, H, h) [61] 1.5 nM (s, H, r) [61] 4.4 nM (s, H, m) [61] |
50,000 nM (s, H, h) [61] | 2427 nM (s, H, h) [61] | |
| Hl1a | 7 | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] | No inhibition (s, HT, h) [123] |
2190 nM (s, ND7/23 cell, h) [123] | 3760 nM (s, rat DRG) [123] | |
| GpTx-1 | 1 | 6000 nM (s, H, h, FLIPR) [122] | 5000 nM (s, H, h, FLIPR) [122] | 20 nM (s, C, h) [76] 22,000 nM (s, H, h, FLIPR) [122] |
301 nM (s, H, h, Manual ephys) [76] 200 nM (HEK293, h, synthetic, PatchXpress) [76] 326,000 nM (s, H, h, FLIPR) [122] |
4200 nM (s, H, h, Manual ephys) [76] >10,000 nM (s, H, h, PatchXpress) [76] 140,000 nM (s, H, h, FLIPR) [122] |
17,000 nM (s, H, h, FLIPR) [122] | 4.4 nM (s, H, h, Manual ephys) [76] 10 nM (s, H, h, PatchXpress) [76] 580 nM (s, H, h, FLIPR) [122] 8 nM, open/inactivated state; 13 nM, closed/resting state (s, C, h,) [122] |
12,200 nM (s, C, h, Manual ephys) [76] 68,000 nM (s, H, h, FLIPR) [122] |
||
| F5A-M6F-T26L-K28R-GpTx-1 | 1 | 1900 nM (s, H, h, PatchXpress) [76] | >10,000 nM (s, H, h, PatchXpress) [76] | 1.6 nM (s, H, h, PatchXpress) [76] | |||||||
| Df1a | 2 | 14.3 nM, s-NH2; 30.7 nM, s-OH; (H, h) [92] |
1.9 nM, s-NH2; 3 nM, s-OH; (H, h) [92] |
3 nM, s-NH2; 10 nM, s-OH; (H, h) [92] | 24 nM, s-NH2; 53.6 nM, s-OH; (H, h) [92] | 45.3 nM, s-NH2; 125.6 nM, s-OH; (H, h) [92] | 7.6 nM, s-NH2; 23 nM, s-OH; (C, h) [92] | 1.9 nM, s-NH2; 60.5 nM, s-OH; (H, h) [92] | |||
| Phlo1a | 2 | 459 nM (n, X, h) [240] | |||||||||
| Phlo1b | 2 | 360 nM (n, X, h) [240] | |||||||||
| Phlo2a | 3 | 404 nM (n, X, h) [240] |
218 nM (n, X, h) [240] |
333 nM (n, X, h) [240] | |||||||
| GrTx-1 | 3 | 630 nM (n, H, h) [241] | 230 nM (n, H, h) [241] |
770 nM (n, H, h) [241] |
1290 nM (n, HT, h) [241] |
~22,000 nM (n, H, h) [241] | 630 nM (n, H, h) [241] |
370 nM (n, HT, h) [241] | |||
| GsAFII | 3 | 5700 nM (n, H, h) [241] | 12,000 nM (n, H, h) [241] | 24,000 nM (n, H, h) [241] | 4000 nM (n, HT, h) [241] |
~42,000 nM (n, H, h) [241] | 6600 nM (n, H, h) [241] |
1030 nM (n, HT, h) [241] |
Note: s:- synthetic; n:- native; rec:- recombinantly expressed; rec-G:- recombinantly expressed with an extra N-terminal Glycine; s-OH:- synthetic free carboxyl end; s-NH2:- synthetic C-terminal amidated; H:- HEK 293 cells; HT:- transiently transfected HEK 293 cells; X:- Xenopus oocytes; C:- CHO cells; S:- SHSY5Y cells; h:- human NaV; r:- rat NaV; m:- mouse NaV; r:- rat NaV; M:- mammalian NaV; FLIPR:- Fluorescence Imaging Plate Reader.