The channel, per se, is more than just a continuous regular channel ensuring the free passage of small hydrophilic molecules [1,2]. An important feature is an internal eyelet region formed by a long loop bent into the channel with its carboxy-negative cluster facing the positive charges from Arg/Lys residues derived from β-sheets belonging to the β-barrel wall. This special organisation creates an electrostatic field in the lumen that regulates the diffusion of the molecule through the constriction area. The functional parameters of the channel have now been well-documented using several techniques including reconstitution in artificial membranes, planar lipid bilayers, patch clamp and ‘liposome swelling’ approaches . Electrophysiological studies provided extensive information concerning the size, conductance, selectivity and voltage gating of the channel characteristics, and yield a functional model of the pore protein inserted in the outer membrane. The role played by internal domains of pore structure during diffusion has been thoroughly investigated using different techniques. Channel size has been evaluated using polyamines as pore-blockers, molecular dynamics, computer simulations focusing on the loop flexibility, and atomic force microscopy investigations, probing the pH-induced channel closure of E. coli OmpF. These data support a new molecular understanding of pore function that is interactive and flexible. To determine the contribution of specific regions in these processes, various pore mutants have been isolated from the environment, chemically generated by random mutagenesis, or recently constructed from site-directed mutagenesis. The different studies carried out on these modified porins, mainly focusing on OmpC, OmpF, PhoE and LamB, highlighted the role of residues belonging to the lumen, or close to amino acids interacting with ones located in the channel. Several mutations have clearly demonstrated the strategic role of charged residues located inside the eyelet of OmpF porin: when some residues located inside the lumen, e.g. amino acids 16, 42, 82 and 119, were substituted, nutrient uptake or antibiotic susceptibility were severely altered (for example see [10–13]).
In addition, recent electrophysiological analyses have demonstrated that the excretion of endogenous cadaverin through porin can mimic a pore-blocker, similarly to external added polyamine . This indicates that modulation of the pore closure can take place in growing bacterial cells in response to external stimuli such as acidic stress or charged compounds. This mechanism may play a prominent role during in vivo resistance towards chemical shocks, hydrophilic antibiotics such as β-lactams or fluoroquinolones.