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Cholesterol modulates amiodarone-membrane interactions in model and native membranes.
Maria C Antunes-Madeira1, Romeu A Videira, Vítor M C Madeira
1Centro de Neurociências e Biologia Celular, Departamento de Zoologia, Universidade de Coimbra, Portugal.
Applied Biochemistry and Biotechnology
|March 21, 2002
Summary
Cholesterol concentration significantly alters how amiodarone affects cell membranes. Higher cholesterol levels can reverse amiodarone
Area of Science:
- Biochemistry
- Membrane Biophysics
- Pharmacology
Background:
- Cholesterol is a key lipid in cell membranes.
- Amiodarone is an antiarrhythmic drug with membrane-interactive properties.
Purpose of the Study:
- To investigate how cholesterol affects amiodarone's interaction with lipid bilayers.
- To understand amiodarone's effects on membrane structure in relation to cholesterol content.
Main Methods:
- Utilized synthetic dimyristoylphosphatidylcholine (DMPC) lipid models.
- Employed fluorescence polarization with DPH and DPH-PA probes.
- Examined amiodarone's effects in native mitochondrial and brain microsome membranes.
Main Results:
- Cholesterol increased molecular order in DMPC bilayers.
- Amiodarone's ordering effects diminished with increasing cholesterol concentrations.
- At high cholesterol levels (>25-30 mol%), amiodarone shifted from ordering to disordering effects.
- Results in native membranes correlated with synthetic models.
Conclusions:
- Cholesterol concentration critically modulates amiodarone's effects on lipid bilayers.
- These findings suggest cholesterol influences amiodarone's action in sarcolemma.