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Effects of Amiloride, an Ion Channel Blocker, on Alamethicin Pore Formation in Negatively Charged, Gold-Supported, Phospholipid Bilayers: A Molecular View

Abbasi, Fatemeh, Su, ZhangFei, Alvarez-Malmagro, Julia, Leitch, J. Jay, Lipkowski, Jacek
Langmuir 2019 v.35 no.14 pp. 5060-5068
alamethicin, atomic force microscopy, dielectric spectroscopy, electrostatic interactions, ion channels, phospholipids, photons
The effects of amiloride on the structure and conductivity of alamethicin ion pore formation within negatively charged, gold-supported, 1,2-dimyristoyl-sn-glycero-3-phosphocholine/Egg-PG membranes were investigated with the help of electrochemical impedance spectroscopy (EIS), photon polarization modulation-infrared reflection spectroscopy (PM-IRRAS), and atomic force microscopy (AFM). The EIS results indicate that ion conductivity across negatively charged phospholipid bilayers containing alamethicin decreases by an order of magnitude when amiloride is introduced to the system. Despite the reduction in ion conductivity, the PM-IRRAS data shows that amiloride does not inhibit ion channel formation by alamethicin peptides. High-resolution AFM images revealed that amiloride enlarges and distorts the shape of alamethicin ion pores when introduced to the system, indicating that it is inserting itself into the mouth of the alamethicin pores. This effect is driven by electrostatic interactions between positively charged amiloride molecules and the negative charge on the membrane.