pH-Dependent properties of ion channels formed by N-terminally glutamate substituted gramicidin A in planar lipid bilayers.

Dmitry K Chistyulin, Tatyana I Rokitskaya, Sergey I Kovalchuk, Alexandra I Sorochkina, Alexander M Firsov, Elena A Kotova, Yuri N Antonenko

Biochimica et biophysica acta 2017 May

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The N-terminally glutamate substituted analogue of the pentadecapeptide gramicidin A [Glu1]gA has been previously described as a low-toxic uncoupler of mitochondrial oxidative phosphorylation and neuroprotector. Here, we studied ion channel-forming activity of this peptide in planar bilayer lipid membranes (BLMs). [Glu1]gA exhibited an ability to induce both macroscopic current and single channels in a broad pH range, albeit with a lower potency than the parent gramicidin A (gA). Single-channel recordings in 1M KCl at pH about 4 showed channel openings of one type with the conductance (about 26pS), similar to that of gA, and the lifetime (40ms), much shorter than that of gA. By contrast, two populations of channels were found at pH9, one of which had much longer duration (several seconds) and lower conductance (3.5-10pS). Autocorrelation function of the current noise of [Glu1]gA revealed a marked shift towards longer correlation times upon alkalinization. The sensitized photoinactivation technique also revealed substantial differences in [Glu1]gA conducting properties at alkaline and acidic pH, in particular deceleration of the photoinactivation kinetics and a sharp decrease in its amplitude upon alkalinization. A double-logarithmic plot of the concentration dependence of [Glu1]gA-induced BLM conductance had the slope of about 3, which pointed to peptide aggregation in the membrane. The data were discussed in relation to pH-dependent aggregation of [Glu1]gA, resulting from deprotonation of the glutamate side chain at alkaline pH. Copyright © 2017 Elsevier B.V. All rights reserved.

Citation

Dmitry K Chistyulin, Tatyana I Rokitskaya, Sergey I Kovalchuk, Alexandra I Sorochkina, Alexander M Firsov, Elena A Kotova, Yuri N Antonenko. pH-Dependent properties of ion channels formed by N-terminally glutamate substituted gramicidin A in planar lipid bilayers. Biochimica et biophysica acta. 2017 May;1859(5):896-902