Effects of Cholesterol-Depleting Agent Methyl-β-Cyclodextrin on the Functional State of Brain Nerve Terminals
Cholesterol acceptor methyl-β-cyclodextrin (MβCD) (15 mM) reduced the cholesterol content in brain nerve terminals (synaptosomes) by one quarter. The application of MβCD to the synaptosomes as well as isolated synaptic vesicles led to the gradual leakage of the protons from the vesicles, as shown by acridine orange fluorescence measurements, whereas the application of MβCD complexed with cholesterol (15:0.2) that increased the membrane cholesterol content stimulated additional vesicle acidification. It was supposed that cholesterol depletion of the plasma membrane with MβCD induced the removal of cholesterol from the membranes of synaptic vesicles resulting in immediate dissipation of synaptic vesicle proton gradient, and so could provoke redistribution of the neurotransmitter between the vesicular and cytosolic pools.
KeywordsSynaptic Vesicle Acridine Orange Proton Gradient Vesicle Acidification Cholesterol Depletion
- Krisanova N, Sivko R, Kasatkina L, Borisova T (2012) Neuroprotection by lowering cholesterol: a decrease in membrane cholesterol content reduces transporter-mediated glutamate release from brain nerve terminals. Biochim Biophys Acta 1822:1013–1023Google Scholar