Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models

Ana R. Santa-Maria, Fruzsina R. Walter, Sándor Valkai, Ana Rita Brás, Mária Mészáros, András Kincses, Adrián Klepe, Diana Gaspar, Miguel A.R.B. Castanho, L. Zimányi, A. Dér, Mária A. Deli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1579-1591
Number of pages13
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number9
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Biological membranes
Surface charge
Lidocaine
Blood-Brain Barrier
Cell culture
Permeability
Endothelial cells
Membranes
Endothelial Cells
Brain
Purple Membrane
Bacteriorhodopsins
Molecules
Halobacterium salinarum
Glycocalyx
Proton Pumps
P-Glycoprotein
Zeta potential
Cell membranes
Membrane Lipids

Keywords

  • Bacteriorhodopsin
  • Blood-brain barrier
  • Brain endothelial cells
  • Lidocaine
  • Permeability
  • Surface charge

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models. / Santa-Maria, Ana R.; Walter, Fruzsina R.; Valkai, Sándor; Brás, Ana Rita; Mészáros, Mária; Kincses, András; Klepe, Adrián; Gaspar, Diana; Castanho, Miguel A.R.B.; Zimányi, L.; Dér, A.; Deli, Mária A.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1861, No. 9, 01.09.2019, p. 1579-1591.

Research output: Contribution to journalArticle

Santa-Maria, AR, Walter, FR, Valkai, S, Brás, AR, Mészáros, M, Kincses, A, Klepe, A, Gaspar, D, Castanho, MARB, Zimányi, L, Dér, A & Deli, MA 2019, 'Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models', Biochimica et Biophysica Acta - Biomembranes, vol. 1861, no. 9, pp. 1579-1591. https://doi.org/10.1016/j.bbamem.2019.07.008
Santa-Maria, Ana R. ; Walter, Fruzsina R. ; Valkai, Sándor ; Brás, Ana Rita ; Mészáros, Mária ; Kincses, András ; Klepe, Adrián ; Gaspar, Diana ; Castanho, Miguel A.R.B. ; Zimányi, L. ; Dér, A. ; Deli, Mária A. / Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models. In: Biochimica et Biophysica Acta - Biomembranes. 2019 ; Vol. 1861, No. 9. pp. 1579-1591.
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AU - Brás, Ana Rita

AU - Mészáros, Mária

AU - Kincses, András

AU - Klepe, Adrián

AU - Gaspar, Diana

AU - Castanho, Miguel A.R.B.

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N2 - 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.

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