Proton conductance through phospholipid bilayers: water wires or weak acids?

Area of Science:

• Membrane biophysics
• Ion transport mechanisms
• Physical chemistry

Background:

• Proton/hydroxide (H+/OH-) permeability across phospholipid bilayers significantly exceeds ion permeability at neutral pH.
• The precise mechanisms governing this high H+/OH- transport remain largely unknown.
• Understanding H+/OH- transport is crucial for cellular physiology and bioenergetics.

Purpose of the Study:

• To review and characterize proton/hydroxide (H+/OH-) permeability and conductance in various planar phospholipid bilayer membranes.
• To investigate factors influencing H+/OH- transport, including pH, inhibitors, enhancers, and membrane composition.
• To elucidate the underlying mechanisms of H+/OH- transport.

Main Methods:

• Analysis of proton/hydroxide (H+/OH-) conductance (GH/OH) measurements in phospholipid bilayers.
• Examination of the effects of inhibitors (e.g., serum albumin, phloretin) and enhancers (e.g., fatty acids, gramicidin) on GH/OH.
• Comparison of GH/OH characteristics in unmodified bilayers versus those modified with fatty acids or gramicidin.

Main Results:

• At pH 7, H+/OH- conductances (GH/OH) range from 2-6 nS cm-2, indicating high permeability.
• Specific molecules like serum albumin and glycerol inhibit GH/OH, while fatty acids and gramicidin can enhance it.
• Water permeability does not correlate with GH/OH, suggesting distinct transport pathways.

Conclusions:

• The high proton/hydroxide (H+/OH-) conductance in unmodified bilayers is likely mediated by weakly acidic contaminants acting as proton carriers.
• In gramicidin-containing membranes, GH/OH characteristics differ significantly, suggesting water wire involvement.
• Residual GH/OH under specific conditions may involve water wires, hydrated defects, or alternative mechanisms.