Desensitization Mechanism in Prokaryotic Ligand-gated Ion Channel

• DOI: 10.1074/jbc.m112.348045
• Publication Date: 2012-04-04T00:43:14Z
• Authors: Phanindra Velisetty; Sudha Chakrapani
• Keywords: Cys-loop receptors

Crystal structures of Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated prokaryotic homologue pentameric (LGIC) from G. violaceus, have provided high-resolution models the architecture and its role in selective conduction drug binding. However, it is still unclear which functional states LGIC gating scheme these crystal represent. Much this uncertainty arises lack thorough understanding properties channels. To elucidate molecular events that constitute gating, we carried out an extensive characterization GLIC function dynamics reconstituted proteoliposomes by patch clamp measurements EPR spectroscopy. We find channels show rapid activation upon jumps to acidic pH followed time-dependent loss conductance because desensitization. desensitization strongly coupled modulated voltage, permeant ions, pore-blocking drugs, membrane cholesterol. Many are parallel functions observed members eukaryotic LGIC. Conformational changes loop C, measured site-directed spin labeling spectroscopy, reveal immobilization during analogous acetylcholine binding protein. Together, our studies suggest conservation mechanistic aspects among LGICs origin.