Screws And Helices

Abstract

In this chapter we begin to deal with the question, How does the change of a voltage across the membrane become the trigger for a configurational change of the channel that drastically alters its conduction properties? We begin with a critical analysis of a conventional model, the screw-helical gating model. Continuing the discussion of systems to the membrane and its ion channels. We review the model of a dissipative structure in excitable membranes, which was proposed long before the isolation of voltage-sensitive ion channels. We then examine the structure, electrical properties and dynamics of the helix. This interesting structure, which constitutes the major portion of an ion channel, 1. THE SCREW-HELICAL GATING HYPOTHESIS We recall that the S4 transmembrane segments of sodium, potassium and calcium channels contain four to eight positively charged residues, separated from one another by two uncharged residues. In the screw-helical gating hypothesis, these voltage sensors are postulated to move by advancing and rotating like a screw, advancing one unit of helical pitch for every 360° of rotation. In conventional terms the question is posed, By what mechanism does the activation gate couple with the voltage? After DNA sequencing had shown that the 1:3 spacing of positive charges on the S4 subunit was a conserved feature of voltage-sensitive ion channels, it became clear that this transmembrane segment must somehow interact with the electric field. In 1986 H. Robert Guy and P. Seetharamulu 1 and William Catterall 2 proposed that, under a depolarization, the electric charges on S4 will experience an outward force that will drive the segment outward in a helical motion. Negative residues in subunits S2 and S3 partially neutralize the positive charges in S4, and could help stabilize the S4 subunit at discrete positions. In a 60° rotation the S4 would advance 0.45 nm outward, and each positive charge would move up to pair with a different negative charge on the neighboring segments. Three such steps would transfer three unit positive charges across the membrane, projecting an arginine residue 1.35 nm into the external aqueous region. In this way the regularity of the spacing of critical phenomena of Chapter 15, we apply the concept of spontaneous order in open is capable of carrying solitons, and of conducting electrons and ions.