Table 1.

Naturally Occurring Amino Acid Replacements That Enhance Sodium Channel Resistance to TTX and STX

Mutation		Known From	Toxin Resistance
Domain I aromatic-to-nonaromatic	D(F/Y)WEN	Pufferfishesa–c, Cynops newtsd, 3 mammalian channelse, f	Depending on replacement, ∼190- to 2,000-fold for TTX/STXa–e,g
Domain II Glu-Asp	EWIET	Tetraodon Nav1.4ba, also soft-shell clam Mya arenariah	STX: ∼3,000-foldh
Domain II Thr-Ser or -Asn	EWIET	Pufferfish and mammal channels with Domain I nonaromatic	Unknown
Domain III Met-Thr	KGWMD	Several pufferfish genes, also flatworm Bdelloura candidaa,i	TTX: 15.2-fold STX: 15-fold
Domain IV Ala-Gly	AGWDG	Several pufferfish genes, flatworm B. candidaj, and Nav1.1La in Danio rerio	TTX: 1.5-fold STX: 11-fold
Domain IV Ile	I1561k	Pufferfish Nav1.6b and Nav1.4a, also Thamnophis garter snakesk	TTX: 2- to 5-foldk
Domain IV Asp-Asn	AGWDG	Canthigaster Nav1.4b, also some Thamnophis garter snakesk	TTX: ∼300-foldl

^aVenkatesh et al. (2005).

^bYotsu-Yamashita et al. (2000).

^cSoong and Venkatesh (2006).

^dKaneko et al. (1997).

^eSatin et al. (1992).

^fCummins et al. (1999).

^gTerlau et al. (1991).

^hBricelj et al. (2005).

ⁱBlair and Anderson (1993).

^jJeziorski et al. (1997).

^kGeffeney et al. (2005).

^lChoudhary et al. (2003).