Attenuation of Proton Currents by Methanol in a Dioxolane-Linked Gramicidin A Channel in Different Lipid Bilayers

Abstract

The mobility of protons in a dioxolane-linked gramicidin A channel (D1) is comparable to the mobility of protons in aqueous solutions (Cukierman, S., E. P. Quigley, and D. S. Crumrine. 1997. Biophys. J. 73:2489-2502). Aliphatic alcohols decrease the mobility of H+ in aqueous solutions. In this study, the effects of methanol on proton conduction through D1 channels were investigated in different lipid bilayers and at different HCl concentrations. Methanol attenuated H+ currents in a voltage-independent manner. Attenuation of proton currents was also independent of H+ concentrations in solution. In phospholipid bilayers, methanol decreased the single channel conductance to protons without affecting the binding affinity of protons to bilayers. In glycerylmonooleate membranes, the attenuation of single channel proton conductances qualitatively resembled the decrease of conductivities of HCl solutions by methanol. However, in both types of lipid bilayers, single channel proton conductances through D1 channels were considerably more attenuated than the conductivities of different HCl solutions. This suggests that methanol modulates single proton currents through D1 channels. It is proposed that, on average, one methanol molecule binds to a D1 channel, and attenuates H+ conductance. The Gibbs free energy of this process (DeltaG0) is approximately 1.2 kcal/mol, which is comparable to the free energy of decrease of HCl conductivity in methanol solutions (1.6 kcal/mol). Apolar substances like urea and glucose that do not transport protons in HCl solutions and do not permeate D1 channels decreased solution conductivity and single channel conductance by a considerably larger proportion than methanol. Cs+ currents through D1 channels were considerably less (fivefold) attenuated by methanol than proton currents. It is proposed that methanol partitions inside the pore of gramicidin channels and delays the transfer of protons between water and methanol molecules, causing a significant attenuation of the single channel proton conductance. Gramicidin channels offer an interesting experimental model to study proton hopping along a single chain of water molecules interrupted by a single methanol molecule.

Conductivity Properties of Thiourea- And Urea-Halogen Inclusion Compounds With Diquinuclidinium Cation as Guest

“…For that we suggest that in the case of large single crystals the role of the water is to repair defects in the relatively fragile lattice, allowing the appearance of macroscopic long-range effects.. The Grotthuss mechanism can be applied to some extent to these systems, 24,25 where water in the supramolecular compounds can be aligned forming polarized chains leading to an additional cooperative mechanism of the conductivity properties due to the presence of polarized water molecules. Proton transfer can produce an electric current when these water molecules instantly connect their fragments through the matrix network, as a result of which preferential conductivity properties in the parallel orientation are observed.…”

The transfer of protons in water wires inside proteins

“…In the top graph of figure 17, measurements of 1 M HCl conductivity (λ, green symbols) and g H in the SS channel (red symbols) have been plotted as a function of the concentration of methanol in solution (127). In the bottom graph, these measurements were normalized to the values of λ and g H in the absence of methanol.…”

“…g H is considerably more attenuated than λ by methanol. The line connecting the g H points is based on a model in which one methanol molecule on average partitions inside the pore of the SS channels and 'blocks' I H (127). The basic mechanisms by which methanol attenuates proton transfer in gA channels remains elusive (85,129).…”

“…Our laboratory has demonstrated that in the dioxolane-linked gA channels protons are transferred. This transfer is modulated by various factors including the stereochemistry of the dioxolane, the nature of the lipid bilayer, and the access resistances to proton entry and exit in the channels (30,78,(80)(81)(82)(85)(86)(87)94,120,127,144).…”

Proton Transfer in Gramicidin Water Wires in Phospholipid Bilayers: Attenuation by Phosphoethanolamine

“…Moreover, proton transfer can be measured in a single channel molecule. Recent work from our laboratory (10)(11)(12)16,(22)(23)(24) have used the SS and RR diastereoisomers of dioxolane-linked gA channels (16,25) to measure H 1 transfer in water wires, and to correlate those experimental measurements with possible molecular mechanisms (16,26). It was suggested that the chiral centers of the dioxolane linker underlie the profound quantitative and qualitative differences in the rate of H 1 transfer in distinct gA channels.…”