The ionic selectivity of large protein ion channels

Biochemistry Research International, 2012

Electrophysiological characterization of large protein channels, usually displaying multi-ionic transport and weak ion selectivity, is commonly performed at physiological conditions (moderate gradients of KCl solutions at decimolar concentrations buffered at neutral pH). We extend here the characterization of the OmpF porin, a wide channel of the outer membrane of E. coli, by studying the effect of salts of divalent cations on the transport properties of the channel. The regulation of divalent cations concentration is essential in cell metabolism and understanding their effects is of key importance, not only in the channels specifically designed to control their passage but also in other multiionic channels. In particular, in porin channels like OmpF, divalent cations modulate the efficiency of molecules having antimicrobial activity. Taking advantage of the fact that the OmpF channel atomic structure has been resolved both in water and in MgCl 2 aqueous solutions, we analyze the single channel conductance and the channel selectivity inversion aiming to separate the role of the electrolyte itself, and the counterion accumulation induced by the protein channel charges and other factors (binding, steric effects, etc.) that being of minor importance in salts of monovalent cations become crucial in the case of divalent cations.

Bio-, Micro-, and Nanosystems (IEEE Cat. No.03EX733), 2003

Ion channels are proteins with a hole down their middle that control an enormous range of biological function. Channels are devices in the engineering sense of the word and engineering analysis helps understand their function. In particular, the current through channels is driven by the power supply of concentration gradient and electrical potential maintained by across membranes by cell metabolism. The current is controlled by the physics of ion permeation in a narrow charged tube. The wall of the tube contains a few fixed charges; the tube is less than 1 nm in diameter. The density of charge (mobile or fixed) in the tube is enormous, ∼10 molar. (Liquid water is ∼55 molar.) Movement of ions through this tube can be well described as the movement of charged spheres according to the Poisson-Drift-Diffusion equations of computational electronics. Selfconsistent computation of the electric field is a necessity. The chemical specificity of channels seems to arise from the crowding of charge in their narrow tunnel. A purely physical description of the energetics of crowded spheres is enough to explain the complex patterns of selectivity found in several types of channels.

2016

Ion channels are specific proteins present in the membranes of living cells. They control the flow of specific ions through a cell, initiated by an ion channel's electrochemical gradient. In doing so, they control important physiological processes such as muscle contraction and neuronal connectivity, which cannot be properly activated if these channels go haywire, leading to life-threatening diseases and psychological disorders. Here, we will develop a generalized microscopic theory of ion selectivity applicable to KcsA, NavRh and Cav (L-type) ion channels. We unambiguously expose why and how a given ion-channel can be highly selective, and yet has a conductance of the order of one million ions per second, or higher. We will identify and prove the correct physico-biochemical mechanisms that are responsible for the high selectivity of a particular ion in a given ion channel. The above mechanisms consist of five conditions, which can be directly associated to these parameters-(i) dehydration energy, (ii) concentration of the "correct" ions (iii) Coulomb-vander-Waals attraction, (iv) pore and ionic sizes, and indirectly to (v) the thermodynamic stability and (vi) the "knock-on" assisted permeation.

2012

Ion channels are specific proteins present in the membranes of living cells. They control the flow of specific ions through a cell, initiated by an ion channel's electrochemical gradient. In doing so, they control important physiological processes such as muscle contraction and neuronal connectivity, which cannot be properly activated if these channels go haywire, leading to life-threatening diseases and psychological disorders. Here, we will develop a generalized microscopic theory of ion selectivity applicable to KcsA, NavRh and Cav (L-type) ion channels. We unambiguously expose why and how a given ion-channel can be highly selective, and yet has a conductance of the order of one million ions per second, or higher. We will identify and prove the correct physico-biochemical mechanisms that are responsible for the high selectivity of a particular ion in a given ion channel. The above mechanisms consist of five conditions, which can be directly associated to these parameters-(i) dehydration energy, (ii) concentration of the "correct" ions (iii) Coulomb-vander-Waals attraction, (iv) pore and ionic sizes, and indirectly to (v) the thermodynamic stability and (vi) the "knock-on" assisted permeation.

Journal of Statistical Mechanics: Theory and Experiment, 2016

The highly selective permeation of ions through biological ion channels can be described and explained in terms of fluctuational dynamics under the influence of powerful electrostatic forces. Hence valence selectivity, e.g. between Ca 2+ and Na + in calcium and sodium channels, can be described in terms of ionic Coulomb blockade, which gives rise to distinct conduction bands and stop-bands as the fixed negative charge Q f at the selectivity filter of the channel is varied. This picture accounts successfully for a wide range of conduction phenomena in a diversity of ion channels. A disturbing anomaly, however, is that what appears to be the same electrostatic charge and structure (the so-called EEEE motif) seems to select Na + conduction in bacterial channels but Ca 2+ conduction in mammalian channels. As a possible resolution of this paradox it is hypothesised that an additional charged protein residue on the permeation path of the mammalian channel increases | | Q f by e, thereby altering the selectivity from Na + to Ca 2+ . Experiments are proposed that will enable the hypothesis to be tested.

Applied Physics Letters, 2013

We show experimentally and theoretically that significant currents can be obtained with a biological ion channel, the OmpF porin of Escherichia coli, using zero-average potentials as driving forces. The channel rectifying properties can be used to pump potassium ions against an external concentration gradient under asymmetric pH conditions. The results are discussed in terms of the ionic selectivity and rectification ratio of the channel. The physical concepts involved may be applied to separation processes with synthetic nanopores and to bioelectrical phenomena. V C 2013 AIP Publishing LLC.[http://dx.

Frontiers in Bioscience, 2003

Physical Review E, 2010

We report charge inversion within a nanoscopic biological protein ion channel in salts of multivalent ions. The presence of positive divalent and trivalent counterions reverses the cationic selectivity of the OmpF channel, a general diffusion porin located in the outer membrane of E. coli. We discuss the conditions under which charge inversion can be inferred from the change in sign of the measured quantity, the channel zero current potential. By comparing experimental results in protein channels whose charge has been modified after site-directed mutagenesis, the predictions of current theories of charge inversion are critically examined. It is emphasized that charge inversion does not necessarily increase with the bare surface charge density of the interface and that even this concept of surface charge density may become meaningless in some biological ion channels. Thus, any theory based on electrostatic correlations or chemical binding should explicitly take into account the particular structure of the charged interface.

International journal of molecular sciences, 2012

Ion channels, which are found in every biological cell, regulate the concentration of electrolytes, and are responsible for multiple biological functions, including in particular the propagation of nerve impulses. The channels with the latter function are gated (opened) by a voltage signal, which allows Na(+) into the cell and K(+) out. These channels have several positively charged amino acids on a transmembrane domain of their voltage sensor, and it is generally considered, based primarily on two lines of experimental evidence, that these charges move with respect to the membrane to open the channel. At least three forms of motion, with greatly differing extents and mechanisms of motion, have been proposed. There is a "gating current", a capacitative current preceding the channel opening, that corresponds to several charges (for one class of channel typically 12-13) crossing the membrane field, which may not require protein physically crossing a large fraction of the mem...

Contributions to science, 2016

The transport of ions across single-molecule protein nanochannels is important both in the biological context and in proposed nanotechnological applications. Here we discuss these systems from the perspective of non-equilibrium physics, and in particular, whether the concepts underlying the physics of diffusive and electrokinetic transport can be employed to predict and understand these systems. [Contrib Sci 11(2): 181-188 (2015)]