pH-dependent influence of membrane-incorporated flunarizine on Ca-binding to phosphatidylserine monolayer membranes

Abstract

The pH-dependent 45Ca binding to phosphatidylserine monolayers was investigated. Ca binding increased with increasing pH. Between pH 10 and pH 11 a steep increase of Ca binding could be observed. This increase was interpreted to be due to complex Ca binding opposed to ionic binding at low pH. Flunarizine added to the spreading solution of the monolayer dose dependently displaced up to 100% Ca at pH 5 independently of phospholipid packing. At pH 11 less than 20% of Ca could be displaced by flunarizine. Intermediate results were found at pH 7. Flunarizine displaced less Ca from dense than from loosely packed monolayers at pH 7. The results suggest two binding states of flunarizine: ionic binding at low pH and apolar binding at high pH. The latter is much less effective in displacing Ca from phosphatidylserine monolayers. The Ca displacing properties of charged flunarizine may prevent a deleterious phospholipid reorientation within the membrane induced by the intracellular Ca rise during ischemia.