Voltage sensitive ion channels, minimal size of ordered phases and the evolution of metazoa.

Abstract

The complex electrical, mechanical and optical behavior of a voltage sensitive ion channel (VSIC) requires that the macromolecule possess at least one ordered phase. For an object to support order, it must be of a minimum size to overcome thermal fluctuations. The limiting size of a stable phase, the correlation length, depends on temperature. Converging lines of experimental evidence indicate that the VSIC is a ferroelectric liquid crystal of the blue phase type. Reaching beyond the analogy of a gated pore, the Channel Activation by Electrostatic Repulsion (CAbER) hypothesis (Leuchtag 2022 Biophys J 121(3):92a) postulates that voltage sensitivity arises from polarization due to the induction of dipoles in the branched sidechains of the numerous isoleucine, leucine and valine residues, producing a polar order in the excitable (closed) phase and making it an insulator by compressing and crowding the ion-conducting segments. On threshold depolarization the dipoles collapse into thermal chaos, reducing the macromolecule's dielectric permittivity and thereby increasing the long-range Coulomb repulsions between the conserved positive charges of the four S4 segments, pushing them apart. The consequent relaxation of the S5 and S6 segments allows their core hydrogen bonds to widen and allow permeant ions to enter and percolate stochastically through the membrane. The critical role of VSIC size in the CAbER model has implications for the beginning of multicellularity during the emergence of the Metazoa in the genomic revolution. At about 300 K, the size effect underlies VSIC activation as an order–disorder transition. This property of the size effect implies that the evolution of Metazoa became possible only after the organism's DNA had grown extensive enough to code for ion channels with dimensions larger than the correlation length to sustain an ordered polar, bioferroelectric, phase.