Insight into the Mechanism of Calcium-Induced Blockage of Gramicidin A Ion Channels

Abstract

The interaction of calcium ions with gramicidin A (gA) ion channels represents a fundamental process with significant implications for understanding ion channel regulation in biological membranes. This study employs electrochemical impedance spectroscopy (EIS), surface-enhanced infrared absorption spectroscopy (SEIRAS), and Langmuir trough experiments to unravel the multifaceted mechanism of calcium-induced blockage of gA channels in a DOPC lipid bilayer. The findings reveal that calcium ions interact with the polar headgroups of DOPC lipids, inducing dehydration and increased packing density, which reduce the mobility of gramicidin monomers. Structural analysis highlights significant elongation of the gA helices, weakening of hydrogen bonds, and a shift in the conformational equilibrium towards inactive monomeric forms. These observations challenge the conventional view of calcium ion blockage being solely due to steric hindrance, proposing instead a broader mechanism involving alterations in both the membrane environment and peptide structure. This novel perspective on calcium-ion-induced ion channel modulation provides valuable insights for designing biomimetic systems and developing therapeutic strategies targeting ion channel dysfunction.