Sodium channel functioning based on an octagonal structure model

The complete amino acid sequence of a sodium channel from squid Loligo bleekeri has been deduced by cloning and sequence analysis of the complementary DNA. A unique feature of the squid sodium channel is the 1,522 residue sequence, approximately three-fourths of those of the rat sodium channels I, II and III. On the basis of the sequence, and in comparison with those of vertebrate sodium channels, we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5–6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of alternating segments S2 and S4. The proposed octagonal structure model is contrasted with that of Noda et al. (Nature 320; 188–192, 1986). The octagonal structure model can explain the gating of activation and inactivation, and ion selectivity, as well as the action mechanism of both tetrodotoxin (TTX) and -scorpion toxin (ScTX), and can be applied not only to the sodium channel, but also to the calcium channel, potassium channel and cGMP-gated channel.The authors would like to express our cordial acknowledgments to Dr. Hideo Tani (Kowa) and Drs. Masahiko Fujino and Haruo Onda (Takeda Pharmaceutical) for their kind support for us to utilize their experimental facilities for DNA cloning and as well as for their stimulating and helpful discussions. We also thank Drs. Toshio Iijima, Michinori Ichikawa, Kiyonori Hirota, Messrs. Tadashi Kimura and Osamu Shono and all our colleagues (Supermolecular Science Division, Electrotechnical Laboratory) for their kind support to collect and isolate optic lobes from live squid. We greatly thank Professors Takuji Takeuchi (University of Tohoku) and David Landowne (University of Miami) for their illuminating discussions and valuable comments.