The surface charge of brain endothelial cells forming the blood-brain barrier (BBB)
is highly negative due to phospholipids in the plasma membrane and the glycocalyx.
This negative charge is an important element of the defense systems of the BBB. Lidocaine,
a cationic and lipophilic molecule which has anaesthetic and antiarrhytmic properties,
exerts its actions by interacting with lipid membranes. Lidocaine when administered
intravenously acts on vascular endothelial cells, but its direct effect on brain endothelial
cells has not yet been studied. Our aim was to measure the effect of lidocaine on
the charge of biological membranes and the barrier function of brain endothelial cells.
We used the simplified membrane model, the bacteriorhodopsin (bR) containing purple
membrane of Halobacterium salinarum and culture models of the BBB. We found that lidocaine
turns the negative surface charge of purple membrane more positive and restores the
function of the proton pump bR. Lidocaine also changed the zeta potential of brain
endothelial cells in the same way. Short-term lidocaine treatment at a 10 μM therapeutically
relevant concentration did not cause major BBB barrier dysfunction, substantial change
in cell morphology or P-glycoprotein efflux pump inhibition. Lidocaine treatment decreased
the flux of a cationic lipophilic molecule across the cell layer, but had no effect
on the penetration of hydrophilic neutral or negatively charged markers. Our observations
help to understand the biophysical background of the effect of lidocaine on biological
membranes and draws the attention to the interaction of cationic drug molecules at
the level of the BBB.