[Channel structure and functioning based on octagonal structure model].

Abstract

On the basis of the sequence comparison of squid sodium channel SQSCl with those of other 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 segments S2 and S4 alternately. The proposed octagonal structure model is contrasted with that of Noda et al (Nature 320 : 188-192, 1986) and with Durrel and Guy (Biophys J 62 : 238-250, 1992). The octagonal structure model can explain the gating of activation and inactivation, the ion selectivity, and as well, the action mechanism of both tetrodotoxin (TTX) and a-scorpion toxin (ScTX), and be applied not only to the sodium channel, but also to the calcium channel, potassium channel, cGMP gated channel and further to the inwardly rectifying K channels. However Yan and Horn have discussed voltage dependent S4 movement in sodium channels from the accessibility of methanethiosulfonate (MTSET) to cystein residue which was substituted for the outermost arginine in IVS4 (Neuron 15 : 213-218, 1995), the neutralization of the arginine was revealed not to influence the activation of the channel. It suggest that the residue in the 3rd position of IVS4 is not a part of the voltage sensor located in the membrane. These result suggest that the change of the accessibility might be caused by the change of the covering of the residue rather than the movement of S4.