TTX resistivity of Na+ channel in newt retinal neuron

We examined voltage-dependent, TTX-resistant Na+ channels of newt retina (nRNaCh) electrophysiologically. IC50-TTX value of nRNaCh is more than 20 microM. We determined partial cDNA sequences of nRNaCh restricted to TTX binding sites (SS2 regions of all four repeats). While the amino acid sequences of SS2 regions of repeats II, III and IV of nRNaCh are identical to those of TTX-sensitive Na+ channels, only one amino acid in SS2 of repeat I of nRNaCh is different. nRNaCh have nonaromatic amino acid (Ala) in this site instead of the aromatic amino acid in a case of TTX-sensitive Na+ channels. Many studies suggested that the differences of TTX sensitivity of Na+ channels are decided by whether amino acid in this site is aromatic or not. Therefore nRNaCh acquire their TTX resistivity with the same mechanism as TTX-resistant cardiac Na+ channels do.