Excitable Membrane, Ion Channel, Electrostatics: A Historical Sketch

Abstract

The roughly one-tenth of a volt across an excitable membrane may not seem large, but across a membrane two lipid molecules thick it yields an electric field comparable to one causing atmospheric lightning. Early attempts to explain the physical basis of the nerve impulse modeled its ion currents as stemming from two processes: the movement of ionic charges by the electric field and the ion diffusion due to ion-concentration differences across the membrane. Hampered by its assumptions of constant properties, this classical electrodiffusion model couldn’t explain axonal membrane data. An eclectic approach combining an equation from electrodiffusion theory with elements of cable theory, wave theory and circuit theory—capacitor, batteries, variable conductors—transformed biophysical science with its successful fitting of the action potential's time course. The development of glass pipette electrodes that restrict ion flow to microscopic membrane patches led to the isolation of ion channels, glycoprotein macromolecules that selectively conduct ion currents. Because it's easy to visualize water-filled pores across these macromolecules, fitted with gates that block or allow ion currents across the membrane, they were named voltage-gated ion channels. This approach is challenged because of its: simplistic models of everyday devices, including screws and paddles; assumption of constant channel capacitance; and disregard of electrostatic repulsions between same-charge residues. Genetic engineering techniques brought the discovery of structural features of many such ion channels. One universal feature is a membrane-spanning segment with a regular array of positively charged amino-acid residues. All also contain multiple amino acids whose sidechains fork into two branches. An electrostatic model based on the ion channel's strong similarities to ferroelectric liquid crystals containing branched chains helps explain the depolarization-driven activation of voltage-sensitive ion channels. [See Leuchtag H R (2008) Voltage-Sensitive Ion Channels, Springer; (2017) Biophys. J. 112(3):544a; 112(3):543a-544a; 112(3):464a.]