Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary; Doctoral School of Biology, University of Szeged, Hungary.
Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary.
Biochim Biophys Acta Biomembr. 2019 Sep 1;1861(9):1579-1591. doi: 10.1016/j.bbamem.2019.07.008. Epub 2019 Jul 10.
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.
脑内皮细胞形成血脑屏障 (BBB) 的表面电荷由于质膜和糖萼中的磷脂而高度负电性。这种负电荷是 BBB 防御系统的重要组成部分。利多卡因是一种具有麻醉和抗心律失常特性的阳离子和亲脂性分子，通过与脂质膜相互作用发挥作用。静脉内给予利多卡因作用于血管内皮细胞，但尚未研究其对脑内皮细胞的直接作用。我们的目的是测量利多卡因对生物膜电荷和脑内皮细胞屏障功能的影响。我们使用简化的膜模型、含有盐杆菌紫色膜的菌紫质 (bR) 和 BBB 的培养模型。我们发现利多卡因使紫色膜的负表面电荷更带正电，并恢复质子泵 bR 的功能。利多卡因也以相同的方式改变了脑内皮细胞的 ζ 电位。在治疗相关浓度 10 μM 的短期利多卡因处理不会导致主要的 BBB 屏障功能障碍、细胞形态的实质性变化或 P-糖蛋白外排泵抑制。利多卡因处理降低了阳离子亲脂性分子穿过细胞层的通量，但对亲水性中性或带负电荷标记物的渗透没有影响。我们的观察结果有助于理解利多卡因对生物膜的影响的生物物理背景，并提请注意阳离子药物分子在 BBB 水平的相互作用。
