Two models of the activation of a voltage-sensitive ion channel (VSIC) are competing—the established model of a fixed water-filled pore with a voltage-driven gate and the challenging hypothesis of a glycoprotein macromolecule dilated by variable repulsions between the positively charged residues of its four S4 segments. Let us consider questions that may help us decide which model comes closer to explaining the process by which a VSIC changes from an insulator at high electric field to a stochastic conductor of selected ions on critical reduction of the field: does the VSIC consists of amino acid residues at fixed coordinates or is it pseudocubical with weak hydrogen bonds, changing its size and shape under variable electrostatic forces? Do the branched sidechains of isoleucine, leucine and valine residues form dipoles under the strong resting electric field, making the VSIC a ferroelectric insulator with a high dielectric permittivity? Do the Coulomb repulsions between positively charged arginine and lysine residues of the four S4 segments increase when the dielectric permittivity decreases on critical depolarization? Do membrane-spanning helical segments of the VSIC expand and partially unwind on activation, consistent with the observed rotation of the plane of polarized light during an action potential? Is the dilation of a VSIC, as it undergoes a proteinquake under reduced electrostriction, similar to the transition of a chiral liquid crystal from a thermotropic, ferroelectric, smectic phase to a lyotropic, nonpolar, nematic phase? Do the ion currents across the channel flow through a single fixed water-filled pore or through transient line defects at disordered intersections between parallel S5 and S6 helices? Did multicellular organisms evolve when DNA coded for membrane proteins with gated pores or with arrays of positive charges on interacting S4 segments?
H. Richard Leuchtag (Sun,) studied this question.