Tetrodotoxin blocks voltage-gated sodium channels, which stops nerves and muscles from firing. Rough-skinned newts concentrate it in the skin, and populations vary widely in how much they carry. The only significant predator that regularly eats them is the common garter snake, Thamnophis sirtalis, which has evolved mutations in its own sodium channels that reduce toxin binding.
The pattern across the Pacific Northwest is geographically matched: in regions where garter snakes are highly resistant, local newts are highly toxic, and where snakes are barely resistant, newts carry little toxin. That correspondence is one of the most cited field examples of coevolutionary escalation, though the match is not perfect and some sites are mismatched in either direction.
Two caveats are frequently lost. The newts do not manufacture their toxin in a simple, settled way; evidence points toward bacterial involvement in tetrodotoxin production, and the source is still argued. And resistance costs the snakes speed, so it is not free.