A molecular model of membrane excitability

Abstract

Alamethicin, monazomycin, or EIM induce electrical excitability in lipid bilayers. The voltage-dependent gating displays all the characteristics observed in excitable cells and its basic features can be quantitatively described by the Hodgkin-Huxley equations.A common molecular mechanism of membrane excitation has been postulated.It assumes that in the absence of an electrical field the channel-forming molecules lie at the surface of the membrane. An applied potential tilts them from the surface into the hydrocarbon region of the bilayer. Once in this position the molecules diffuse laterally and form aggregates which act as channels for the flow of ions.ellipsoid with t w o glutamic residues at one end, and a metal ion in four-o r five-fold coordination with peptide carbonyl oxygens at the other. An applied field pulls the cationic end through the membrane t o the other side, while the glutamic residues hold the other end attached t o the original surface. The molecules now span the membrane and aggregate, forming oligomeric channels in which most of the peptide carbonyls face toward the center, and the methyl groups outward. Monomers and dimers do not conduct and an individual channel can have different conductance values depending on the number of monomers in the aggregate and the resulting channel diameter. A quantitative description of this process matches observed gating kinetics, gating currents, and the single channel conductance increments. Without additional assumptions, inactivation follows directly from the aggregation process because with proper rate constants, the average degree of polymerization and therefore number of open channels goes through a maximum in time.In the case of alamethicin we assume that the molecule forms an elongatedThe model may also apply t o the excitation process of higher cells.

A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin

“…These experiments seem to indicate that insertion of peptide aggregates would be voltage dependent and, as soon as the peptides are embedded in the membrane, the mechanism of ion channel formation would become voltage independent. Several mechanisms have been described in the literature to explain membrane permeation by linear ␣-helical peptides (5), namely barrel-stave (26), toroidal pore (27), and carpet-like (28). D1 concentrations necessary for macroscopic and single-channel measurements were very low (Ͻ10 nM) and would not be compatible with the latter one.…”

Structure and dynamics of cationic membrane peptides and proteins: Insights from solid‐state NMR

“…61 For AMPs that disrupt phospholipid and LPS membranes, four main structural models have been proposed: barrel stave, toroidal pore, carpet, and inplane diffusion. 53,62 The barrel-stave model, proposed based on studies of alamethicin, 63,64 posits the formation of TM water-filled pores lined by the amphipathic peptides. Lipid molecules adopt their normal parallel orientation to the bilayer normal, with the acyl chains contacting the hydrophobic part of the amphipathic AMPs.…”

Voltage‐dependent and multi‐state ionic channels induced by trichorzianines, anti‐fungal peptides related to alamethicin

“…These channels consist in aggregates of amphipathic (mostly o~-) helical monomers whose sequential uptake and release (the 'barrelstave' model) leads to the multi-level singleconductance pattern [1,2]. According to the model now in favour [3], at rest, the N-terminal part up to Pro 14 is within the membrane [4], without crossing it totally, whilst the remainder of the molecule lies at the interface.…”