Figure 2. Action of predation- and defence-evoked C. geographus venoms on human receptors.

(a–d) Both predation- (blue) and defence-evoked (green) venoms (1 mg each) were separated on RP-HPLC. The resulting 72 1-min fractions (F1-F72) were screened on SH-SY5Y human neuroblastoma cells for activity at α7 (a,b) and α3-containing nicotinic receptors (c,d), Na_v1.2 and Na_v1.7 voltage-gated sodium channel (e,f) and Ca_v2.2 voltage-gated calcium channel (g,h). Active fractions are highlighted in red on the left panels, with a response ratio >1 indicating greater activity in the defence than the predation-evoked venom, and vice versa (except F32 and F33, which show minor slowing of the response for Nav1.2/7 in both predation- and defence-evoked venoms). Specific responses for active fractions are shown on the right panels (b,d,f and h), and known toxins detected in these fractions are indicated. Whereas the predation-evoked venom only shows full inhibition of Ca_v2.2 response due to trace amount of ω-GVIIA and ω-GVIA, the defence-evoked venom shows potent inhibition of all molecular targets, with several well-characterized toxins identified in the active fractions. The potent block of these key physiological ion channels explains the lethal effect of C. geographus defensive envenomation on humans.