Effect of amiodarone on membrane fluidity and Na+/K+ ATPase activity in rat-brain synaptic membranes.
In rat-brain synaptic membranes at a fixed temperature (37 degrees C), amiodarone dose-dependently inhibits the Na+/K+ ATPase activity (IC50 approximately equal to 2.10(-5)M) and produces a linear increase in the degree of fluorescence depolarization (P) of 1,6-diphenylhexatriene embedded in the lipid matrix. Amiodarone has no effect on Mg++ ATPase and K+PNPase activity up to 3.10(-4)M. Studies carried out at different temperatures indicate that 10(-5)M amiodarone inhibits the Na+/K+ ATPase and decreases the lipid fluidity at all the temperatures studied (9 - 40 degrees C). The compound significantly displaces the temperature of transition observed around 20 degrees C in both Na+/K+ ATPase activity and lipid fluidity to 24 degrees C with no changes in slopes. The results suggest that part of the selective inhibition of Na+/K+ ATPase activity by amiodarone could be due to the effects of the drug on lipid dynamics.
Chatelain
P
P
Laruel
R
R
Gillard
M
M
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology*; D004161:Diphenylhexatriene / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005454:Fluorescence Polarization; D008433:Mathematics; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013570:Synaptic Membranes / Q000201:enzymology*; D013696:Temperature
D001572:Benzofurans; D004161:Diphenylhexatriene; D000254:Sodium-Potassium-Exchanging ATPase; D000638:Amiodarone