Venom from the platypus, Ornithorhynchus anatinus, induces a calcium-dependent current in cultured dorsal root ganglion cells

The platypus (Ornithorhynchus anatinus), a uniquely Australian species, is one of the few living venomous mammals. Although envenomation of humans by many vertebrate and invertebrate species results in pain, this is often not the principal symptom of envenomation. However, platypus envenomation resu lts in an immediate excruciating pain that develops into a very longlasting hyperalgesia. We have previously shown that the venom contains a C-type na triuretic peptide that causes mast cell degranulation, and this probably co ntributes to the development of the painful response. Now we demonstrate th at platypus venom has a potent action on putative nociceptors. Application of the venom to small to medium diameter dorsal root ganglion cells for 10 s resulted in an inward current lasting several minutes when the venom was diluted in buffer at pH 6.1 but not at pH 7.4. The venom itself has a pH of 6.3. The venom activated a current with a linear current-voltage relations hip between -100 and -25 mV and with a reversal potential of -11 mV. Ion su bstitution experiments indicate that the current is a nonspecific cationic current. The response to the venom was blocked by the membrane-permeant Ca2 +-ATPase inhibitor, thapsigargin, and by the tyrosine- and serine-kinase in hibitor, k252a. Thus the response appears to be dependent on calcium releas e from intracellular stores. The identity of the venom component( s) that i s responsible for the responses we have described is yet to be determined b ut is probably not the C-type natriuretic peptide or the defensin-like pept ides that are present in the venom.