Relaxation studies of ion transport systems in lipid bilayer membranes

Läuger, P.; Benz, Roland; Stark, G.; Bamberg, Ernst; Jordan, Peter C.; Fahr, Alfred; Brock, W.

doi:10.1017/s003358350000247x

Cited by 165 publications

(52 citation statements)

References 149 publications

(288 reference statements)

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“…This observation has been explained by a dipolar potential, originating in ordered ester carbonyl groups, which is positive toward the hydrocarbon core (12). Most studies of the kinetics of ion crossing monitor either current relaxations after an applied voltage step or voltage relaxations after a charge pulse (7,9). These techniques, although very useful, are limited by capacitive transients and by ambiguity of interpretation (14).…”

mentioning

confidence: 99%

Photogating of ionic currents across a lipid bilayer.

Drain

Christensen

Mauzerall

1989

Proc. Natl. Acad. Sci. U.S.A.

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Photoformation of metalloporphyrin cations in a lipid bilayer increases the ionic currents of negative and decreases those of positive hydrophobic ions. At low concentrations of the mobile hydrophobic ion, a 30% change in conductivity is observed that decreases with increasing concentration of positive tetraphenylphosphonium ion and increases drastically with increasing concentration of negative tetraphenylboride ion. In the region of saturated conductance of boride ion, the increase in conductivity is 3.6-fold. A 15-fold increase is observed with the protonophore carbonyl cyanide 3-chlorophenylhydrazone. In this case the net charge gated is 300 times greater than the photogenerated charge in the bilayer membrane. Thus there is a net gain in this organic field effect phototransistor. The gating can also be accomplished by continuous light or chemical oxidants. Photogating is explained as space charge effects inside the bilayer.There is great interest in the movement of ions across cell membranes since these currents are associated with the activity ofall metabolically functional cells. In addition, there is much work aimed at understanding the chemical properties ofthese membranes (1). The planar lipid bilayer membrane as developed by Mueller et al. (2) has proven to be remarkably useful as a model ofthe cell membrane. It was discovered that small ions cross these membranes by two mechanisms: ion channels that can be gated by voltage or receptors (3, 4) and ion carriers that are not gated (5). We now show that the latter ionic currents, exemplified by currents of large hydrophobic ions, can be gated by photoinduced charge generation inside the membrane. The photogating effect is explained by local electrostatic effects in the bilayer membrane. The pigment/ bilayer/hydrophobic ion system is an example of an organic field effect phototransistor (6).Much work has been carried out on the mechanism by which ion carriers or hydrophobic ions cross the lipid bilayer (7-11). The large radius of these ionic species decreases the Born electrostatic charging energy of the ion, thus enabling them to traverse the hydrocarbon core of the membrane (10). It is striking that for hydrophobic ions of similar size, the conductivity of negative ions is 102-103 times that of positive ions (7,8,12,13). This observation has been explained by a dipolar potential, originating in ordered ester carbonyl groups, which is positive toward the hydrocarbon core (12). Most studies of the kinetics of ion crossing monitor either current relaxations after an applied voltage step or voltage relaxations after a charge pulse (7,9). These techniques, although very useful, are limited by capacitive transients and by ambiguity of interpretation (14). The present technique avoids the former problem and allows a direct measure of the transients in the change of conductivity. EXPERIMENTALThe 4-ml plastic membrane cell was separated by a Teflon divider with a 1-mm2 hole in the center and had glass slides for windows. A bilayer was formed from a solut...

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mentioning

confidence: 99%

Photogating of ionic currents across a lipid bilayer.

Drain

Christensen

Mauzerall

1989

Proc. Natl. Acad. Sci. U.S.A.

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“…3 (ref . 5) is not certain because the macroscopic assumptions used (8) to determine the parameters that define α da in Eq. 3 are qualitative.…”

Section: Significancementioning

confidence: 99%

Modeling gating charge and voltage changes in response to charge separation in membrane proteins

Kim

Chakrabarty

Brzezinski

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Measurements of voltage changes in response to charge separation within membrane proteins can offer fundamental information on mechanisms of charge transport and displacement processes. A recent example is provided by studies of cytochrome c oxidase. However, the interpretation of the observed voltage changes in terms of the number of charge equivalents and transfer distances is far from being trivial or unique. Using continuum approaches to describe the voltage generation may involve significant uncertainties and reliable microscopic simulations are not yet available. Here, we attempt to solve this problem by using a coarse-grained model of membrane proteins, which includes an explicit description of the membrane, the electrolytes, and the electrodes. The model evaluates the gating charges and the electrode potentials (c.f. measured voltage) upon charge transfer within the protein. The accuracy of the model is evaluated by a comparison of measured voltage changes associated with electron and proton transfer in bacterial photosynthetic reaction centers to those calculated using our coarse-grained model. The calculations reproduce the experimental observations and thus indicate that the method is of general use. Interestingly, it is found that charge-separation processes with different spatial directions (but the same distance perpendicular to the membrane) can give similar observed voltage changes, which indicates that caution should be exercised when using simplified interpretation of the relationship between charge displacement and voltage changes.bacterial reaction center | membrane potential | electrogenicity | proton/electron transfer T he use of electrometric techniques to study time-dependent membrane potentials has been exploited in elucidating charge motions in membrane proteins, thereby offering mechanistic insights into the function of membrane-bound channels and pumps (1). For example, data from time-resolved measurements of voltage changes across the redox-driven proton pump cytochrome c oxidase have been used to propose a sequence of electron and proton-transfer events within the enzyme (2). These studies enabled observation of proton-transfer reactions that are typically "invisible" when using spectroscopic techniques and to link these events to electron-transfer reactions. Unfortunately, a correlation of the observed voltage changes with the number and displacements of transferred charges is challenging because the nature of the dielectric response in a protein-membrane system is complex. Thus, it is not straightforward to use macroscopic models to obtain a unique relationship between internal charge motions and the generated potential. The problem is particularly serious if the dielectric or electrostatic response changes significantly in the time range of the experiment. For example, in the case of cytochrome c oxidase a voltage change may be generated by the relaxation of water molecules in an intraprotein proton pathway approximately perpendicular to the membrane surface in response to an int...

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“…Kinetic Models to Describe Lipid-Bilayer Permeation. -Two models to describe the kinetics of lipid-bilayer permeation will be discussed: a diffusion model following Ficks first law and a flip-flop model, which is based on a three-step mechanism, namely partitioning into one lipid layer, translocation (flip-flop) to the opposite lipid layer, and partitioning out of the opposite lipid layer [2] [3]. Following the diffusion model, no significant permeation of charged compounds across lipid bilayers is expected.…”

Section: Characteristics Of Lipidmentioning

confidence: 99%

Lipid‐Bilayer Permeation of Drug‐Like Compounds

Krämer

Lombardi

Primorac

et al. 2009

Chemistry & Biodiversity

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Lipid-bilayer permeation is determinant for the disposition of xenobiotics in the body. It controls the pharmacokinetic behavior of drugs and is, in many cases, a prerequisite for intracellular targeting. Permeation of in vivo barriers is in general predicted from lipophilicity and related parameters. This article goes beyond the empirical correlations, and elucidates the processes and their interplay determining bilayer permeation. A flip-flop model for bilayer permeation, which considers the partitioning rate constants beside the translocation rate constants, is compared with the diffusion model based on Fick's first law. According to the flip-flop model, the ratios of aqueous volumes to barrier area can determine whether partitioning or translocation is rate-limiting. The flip-flop model allows permeation of anions and cations, and expands our understanding of pH-dependent permeation kinetics. Some experimental evidences for ion-controlled permeation at pH 7 are also included in this work.

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Relaxation studies of ion transport systems in lipid bilayer membranes

Cited by 165 publications

References 149 publications

Photogating of ionic currents across a lipid bilayer.

Photogating of ionic currents across a lipid bilayer.

Modeling gating charge and voltage changes in response to charge separation in membrane proteins

Lipid‐Bilayer Permeation of Drug‐Like Compounds

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